Skip to main content

The Role of Inflammation in Prostate Cancer

  • Chapter
  • First Online:
Inflammation and Cancer

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 816))

Abstract

In the United States and in “Westernized” countries, the prevalence of both prostate cancer and prostate inflammation is very high, indicating that the two pathologies could be causally related. Indeed, chronic inflammation is now regarded as an “enabling” characteristic of human cancer. Prostate cancer incidence is thought to be mediated in part by genetics, but also by environmental exposures, including the same exposures that may contribute to the development of prostatic inflammation. As our understanding of the role of inflammation in cancer deepens, it is increasingly apparent that “inflammation” as a whole is a complex entity that does not always play a negative role in cancer etiology. In fact, inflammation can play potentially dichotomous (both pro and antitumorigenic) roles depending on the nature and the cellular makeup of the immune response. This chapter will focus on reviewing the current state of knowledge on the role of innate and adaptive immune cells within the prostate tumor microenvironment and their seemingly complex role in prostate cancer in preventing versus promoting initiation and progression of the disease.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Aaltomaa S, Lipponen P, Papinaho S, Kosma V (1993) Mast cells in breast cancer. Anticancer Res 13(3):785–788

    CAS  PubMed  Google Scholar 

  • Allavena P, Sica A, Garlanda C, Mantovani A (2008) The Yin-Yang of tumor-associated macrophages in neoplastic progression and immune surveillance. Immunol Rev 222(1):155–161. doi:10.1111/j.1600-065X.2008.00607.x

    CAS  PubMed  Google Scholar 

  • Ammirante M, Luo J-L, Grivennikov S, Nedospasov S, Karin M (2010) B-cell-derived lymphotoxin promotes castration-resistant prostate cancer. Nature 464:302–305. doi:10.1038/nature08782

    CAS  PubMed Central  PubMed  Google Scholar 

  • Andreani V, Gatti G, Simonella L, Rivero V, Maccioni M (2007) Activation of toll-like receptor 4 on tumor cells in vitro inhibits subsequent tumor growth in vivo. Cancer Res 67(21):10519–10527. doi:10.1158/0008-5472.can-07-0079

    CAS  PubMed  Google Scholar 

  • Arock M, Ross E, Lai-Kuen R, Averlant G, Gao Z, Abraham SN (1998) Phagocytic and tumor necrosis factor alpha response of human mast cells following exposure to gram-negative and gram-positive bacteria. Infect Immun 66(12):6030–6034

    CAS  PubMed Central  PubMed  Google Scholar 

  • Barach YS, Lee JS, Zang X (2011) T cell coinhibition in prostate cancer: new immune evasion pathways and emerging therapeutics. Trends Mol Med 17(1):47–55. doi:http://dx.doi.org/10.1016/j.molmed.2010.09.006

  • Barber DL, Wherry EJ, Masopust D, Zhu B, Allison JP, Sharpe AH, Freeman GJ, Ahmed R (2006) Restoring function in exhausted CD8 T cells during chronic viral infection. Nature 439(7077):682–687. doi:http://www.nature.com/nature/journal/v439/n7077/suppinfo/nature04444_S1.html

  • Bauskin AR, Brown DA, Junankar S, Rasiah KK, Eggleton S, Hunter M, Liu T, Smith D, Kuffner T, Pankhurst GJ, Johnen H, Russell PJ, Barret W, Stricker PD, Grygiel JJ, Kench JG, Henshall SM, Sutherland RL, Breit SN (2005) The propeptide mediates formation of stromal stores of PROMIC-1: role in determining prostate cancer outcome. Cancer Res 65(6):2330–2336. doi:10.1158/0008-5472.can-04-3827

    CAS  PubMed  Google Scholar 

  • Berger P, Perng D-W, Thabrew H, Compton SJ, Cairns JA, McEuen AR, Marthan R, Tunon De Lara J-M, Walls AF (2001) Tryptase and agonists of PAR-2 induce the proliferation of human airway smooth muscle cells. J Appl Physiol 91(3):1372–1379

    Google Scholar 

  • Bethel CR, Faith D, Li X, Guan B, Hicks JL, Lan F, Jenkins RB, Bieberich CJ, De Marzo AM (2006) Decreased NKX3.1 protein expression in focal prostatic atrophy, prostatic intraepithelial neoplasia, and adenocarcinoma: association with Gleason score and chromosome 8p deletion. Cancer Res 66(22):10683–10690. doi:10.1158/0008-5472.can-06-0963

    CAS  PubMed  Google Scholar 

  • Bissell MJ, Hines WC (2011) Why don’t we get more cancer? A proposed role of the microenvironment in restraining cancer progression. Nat Med 17(3):320–329. doi:http://www.nature.com/nm/journal/v17/n3/abs/nm.2328.html#supplementary-information

  • Bootcov MR, Bauskin AR, Valenzuela SM, Moore AG, Bansal M, He XY, Zhang HP, Donnellan M, Mahler S, Pryor K, Walsh BJ, Nicholson RC, Fairlie WD, Por SB, Robbins JM, Breit SN (1997) MIC-1, a novel macrophage inhibitory cytokine, is a divergent member of the TGF-β superfamily. Proc Natl Acad Sci 94(21):11514–11519

    CAS  PubMed Central  PubMed  Google Scholar 

  • Breit SN, Johnen H, Cook AD, Tsai VWW, Mohammad MG, Kuffner T, Zhang HP, Marquis CP, Jiang L, Lockwood G, Lee-Ng M, Husaini Y, Wu L, Hamilton JA, Brown DA (2011) The TGF-β superfamily cytokine, MIC-1/GDF15: a pleotrophic cytokine with roles in inflammation, cancer and metabolism. Growth Factors 29(5):187–195. doi:10.3109/08977194.2011.607137

    CAS  PubMed  Google Scholar 

  • Brown DA, Stephan C, Ward RL, Law M, Hunter M, Bauskin AR, Amin J, Jung K, Diamandis EP, Hampton GM, Russell PJ, Giles GG, Breit SN (2006) Measurement of serum levels of macrophage inhibitory cytokine 1 combined with prostate-specific antigen improves prostate cancer diagnosis. Clin Cancer Res 12(1):89–96. doi:10.1158/1078-0432.ccr-05-1331

    CAS  PubMed  Google Scholar 

  • Brown DA, Lindmark F, Stattin P, Bälter K, Adami H-O, Zheng SL, Xu J, Isaacs WB, Grönberg H, Breit SN, Wiklund FE (2009) Macrophage inhibitory cytokine 1: a new prognostic marker in prostate cancer. Clin Cancer Res 15(21):6658–6664. doi:10.1158/1078-0432.ccr-08-3126

    CAS  PubMed Central  PubMed  Google Scholar 

  • Cairns JA, Walls AF (1996) Mast cell tryptase is a mitogen for epithelial cells. Stimulation of IL-8 production and intercellular adhesion molecule-1 expression. J Immunol 156(1):275–283

    CAS  PubMed  Google Scholar 

  • Chan JK, Magistris A, Loizzi V, Lin F, Rutgers J, Osann K, DiSaia PJ, Samoszuk M (2005) Mast cell density, angiogenesis, blood clotting, and prognosis in women with advanced ovarian cancer. Gynecol Oncol 99(1):20–25. doi:http://dx.doi.org/10.1016/j.ygyno.2005.05.042

  • Chen L (2004) Co-inhibitory molecules of the B7-CD28 family in the control of T-cell immunity. Nat Rev Immunol 4(5):336–347

    CAS  PubMed  Google Scholar 

  • Chen Y-C, Giovannucci E, Lazarus R, Kraft P, Ketkar S, Hunter DJ (2005) Sequence variants of toll-like receptor 4 and susceptibility to prostate cancer. Cancer Res 65(24):11771–11778. doi:10.1158/0008-5472.can-05-2078

    CAS  PubMed  Google Scholar 

  • Chen Y-C, Giovannucci E, Kraft P, Lazarus R, Hunter DJ (2007) Association between toll-like receptor gene cluster (TLR6, TLR1, and TLR10) and prostate cancer. Cancer Epidemiol Biomark Prev 16(10):1982–1989. doi:10.1158/1055-9965.epi-07-0325

    CAS  Google Scholar 

  • Cheng L, Wang J, Li X, Xing Q, Du P, Su L, Wang S (2011) Interleukin-6 induces Gr-1+CD11b+ myeloid cells to suppress CD8+ T cell-mediated liver injury in mice. PLoS ONE 6(3):e17631. doi:10.1371/journal.pone.0017631

    CAS  PubMed Central  PubMed  Google Scholar 

  • Cheon EC, Khazaie K, Khan MW, Strouch MJ, Krantz SB, Phillips J, Blatner NR, Hix LM, Zhang M, Dennis KL, Salabat MR, Heiferman M, Grippo PJ, Munshi HG, Gounaris E, Bentrem DJ (2011) Mast cell 5-lipoxygenase activity promotes intestinal polyposis in APCΔ468 mice. Cancer Res 71(5):1627–1636. doi:10.1158/0008-5472.can-10-1923

    CAS  PubMed  Google Scholar 

  • Cheung PK, Woolcock B, Adomat H, Sutcliffe M, Bainbridge TC, Jones EC, Webber D, Kinahan T, Sadar M, Gleave ME, Vielkind J (2004) Protein profiling of microdissected prostate tissue links growth differentiation factor 15 to prostate carcinogenesis. Cancer Res 64(17):5929–5933. doi:10.1158/0008-5472.can-04-1216

    CAS  PubMed  Google Scholar 

  • Chin AI, Miyahira AK, Covarrubias A, Teague J, Guo B, Dempsey PW, Cheng G (2010) Toll-like receptor 3–mediated suppression of TRAMP prostate cancer shows the critical role of type I interferons in tumor immune surveillance. Cancer Res 70(7):2595–2603. doi:10.1158/0008-5472.can-09-1162

    CAS  PubMed Central  PubMed  Google Scholar 

  • Chun JY, Nadiminty N, Dutt S, Lou W, Yang JC, Kung H-J, Evans CP, Gao AC (2009) Interleukin-6 regulates androgen synthesis in prostate cancer cells. Clin Cancer Res 15(15):4815–4822. doi:10.1158/1078-0432.ccr-09-0640

    CAS  PubMed Central  PubMed  Google Scholar 

  • Clemente CG, Mihm MC, Bufalino R, Zurrida S, Collini P, Cascinelli N (1996) Prognostic value of tumor infiltrating lymphocytes in the vertical growth phase of primary cutaneous melanoma. Cancer 77(7):1303–1310. doi:10.1002/(sici)1097-0142(19960401)77:7<1303:aid-cncr12>3.3.co;2-0

    CAS  PubMed  Google Scholar 

  • Coussens LM, Raymond WW, Bergers G, Laig-Webster M, Behrendtsen O, Werb Z, Caughey GH, Hanahan D (1999) Inflammatory mast cells up-regulate angiogenesis during squamous epithelial carcinogenesis. Genes Dev 13(11):1382–1397

    CAS  PubMed Central  PubMed  Google Scholar 

  • Crivellato E, Nico B, Mallardi F, Beltrami CA, Ribatti D (2003) Piecemeal degranulation as a general secretory mechanism? Anat Rec Part A Discov Mol Cell Evol Biol 274A(1):778–784. doi:10.1002/ar.a.10095

    Google Scholar 

  • Dabiri S, Huntsman D, Makretsov N, Cheang M, Gilks B, Bajdik C, Gelmon K, Chia S, Hayes M (2004) The presence of stromal mast cells identifies a subset of invasive breast cancers with a favorable prognosis. Mod Pathol 17(8):1025

    Google Scholar 

  • De Marzo AM (2007) The pathology of human prostatic atrophy and inflammation. In: Chung LK, Isaacs W, Simons J (eds) Prostate cancer. Contemporary Cancer Research. Humana Press, pp 33–48. doi:10.1007/978-1-59745-224-3_2

  • De Marzo AM, Marchi VL, Epstein JI, Nelson WG (1999) Proliferative inflammatory atrophy of the prostate: implications for prostatic carcinogenesis. Am J Pathol 155(6):1985–1992. doi:http://dx.doi.org/10.1016/S0002-9440(10)65517-4

  • De Marzo AM, Platz EA, Sutcliffe S, Xu J, Gronberg H, Drake CG, Nakai Y, Isaacs WB, Nelson WG (2007) Inflammation in prostate carcinogenesis. Nat Rev Cancer 7(4):256–269

    PubMed Central  PubMed  Google Scholar 

  • Delongchamps NB, de la Roza G, Chandan V, Jones R, Sunheimer R, Threatte G, Jumbelic M, Haas GP (2008) Evaluation of prostatitis in autopsied prostates—is chronic inflammation more associated with benign prostatic hyperplasia or cancer? J Urol 179(5):1736–1740. doi:http://dx.doi.org/10.1016/j.juro.2008.01.034

  • Disis ML (2010) Immune regulation of cancer. J Clin Oncol 28(29):4531–4538. doi:10.1200/jco.2009.27.2146

    CAS  PubMed Central  PubMed  Google Scholar 

  • Dotti G (2009) Blocking PD-1 in cancer immunotherapy. Blood 114(8):1457–1458. doi:10.1182/blood-2009-05-223412

    CAS  PubMed  Google Scholar 

  • Dulos J, Carven GJ, van Boxtel SJ, Evers S, Driessen-Engels LJA, Hobo W, Gorecka MA, de Haan AFJ, Mulders P, Punt CJA, Jacobs JFM, Schalken JA, Oosterwijk E, van Eenennaam H, Boots AM (2012) PD-1 blockade augments Th1 and Th17 and suppresses Th2 responses in peripheral blood from patients with prostate and advanced melanoma cancer. J Immunother 35(2):169–178 110.1097/CJI.1090b1013e318247a318244e318247

    Google Scholar 

  • Ebelt K, Babaryka G, Frankenberger B, Stief CG, Eisenmenger W, Kirchner T, Schendel DJ, Noessner E (2009) Prostate cancer lesions are surrounded by FOXP3+, PD-1+ and B7-H1+ lymphocyte clusters. Eur J Cancer 45(9):1664–1672. doi:http://dx.doi.org/10.1016/j.ejca.2009.02.015

  • Edin S, Wikberg ML, Dahlin AM, Rutegård J, Öberg Å, Oldenborg P-A, Palmqvist R (2012) The distribution of macrophages with a M1 or M2 phenotype in relation to prognosis and the molecular characteristics of colorectal cancer. PLoS ONE 7(10):e47045. doi:10.1371/journal.pone.0047045

    CAS  PubMed Central  PubMed  Google Scholar 

  • Ellem SJ, Wang H, Poutanen M, Risbridger GP (2009) Increased endogenous estrogen synthesis leads to the sequential induction of prostatic inflammation (prostatitis) and prostatic pre-malignancy. Am J Pathol 175(3):1187–1199. doi:http://dx.doi.org/10.2353/ajpath.2009.081107

  • Fisher E, Sass R, Watkins G, Johal J, Fisher B (1985) Tissue mast cells in breast cancer. Breast Cancer Res Treat 5(3):285–291. doi:10.1007/bf01806023

    CAS  PubMed  Google Scholar 

  • Fisher ER, Paik SM, Rockette H, Jones J, Caplan R, Fisher B (1989) Prognostic significance of eosinophils and mast cells in rectal cancer: findings from the National Surgical Adjuvant Breast and Bowel Project (protocol R-01). Human Pathol 20(2):159–163. doi:http://dx.doi.org/10.1016/0046-8177(89)90180-9

  • Flammiger A, Bayer F, Cirugeda-Kühnert A, Huland H, Tennstedt P, Simon R, Minner S, Bokemeyer C, Sauter G, Schlomm T, Trepel M (2012) Intratumoral T but not B lymphocytes are related to clinical outcome in prostate cancer. APMIS 120(11):901–908. doi:10.1111/j.1600-0463.2012.02924.x

    CAS  PubMed  Google Scholar 

  • Fleischmann A, Schlomm T, Köllermann J, Sekulic N, Huland H, Mirlacher M, Sauter G, Simon R, Erbersdobler A (2009) Immunological microenvironment in prostate cancer: high mast cell densities are associated with favorable tumor characteristics and good prognosis. Prostate 69(9):976–981. doi:10.1002/pros.20948

    CAS  PubMed  Google Scholar 

  • Forssell J, Öberg Å, Henriksson ML, Stenling R, Jung A, Palmqvist R (2007) High macrophage infiltration along the tumor front correlates with improved survival in colon cancer. Clin Cancer Res 13(5):1472–1479. doi:10.1158/1078-0432.ccr-06-2073

    CAS  PubMed  Google Scholar 

  • Freeman GJ, Long AJ, Iwai Y, Bourque K, Chernova T, Nishimura H, Fitz LJ, Malenkovich N, Okazaki T, Byrne MC, Horton HF, Fouser L, Carter L, Ling V, Bowman MR, Carreno BM, Collins M, Wood CR, Honjo T (2000) Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. J Exp Med 192(7):1027–1034. doi:10.1084/jem.192.7.1027

    CAS  PubMed Central  PubMed  Google Scholar 

  • Frungieri MB, Weidinger S, Meineke V, Köhn FM, Mayerhofer A (2002) Proliferative action of mast-cell tryptase is mediated by PAR2, COX2, prostaglandins, and PPARγ: possible relevance to human fibrotic disorders. Proc Natl Acad Sci 99(23):15072–15077. doi:10.1073/pnas.232422999

    CAS  PubMed Central  PubMed  Google Scholar 

  • Fujita K, Hosomi M, Tanigawa G, Okumi M, Fushimi H, Yamaguchi S (2011) Prostatic inflammation detected in initial biopsy specimens and urinary pyuria are predictors of negative repeat prostate biopsy. J Urol 185(5):1722–1727. doi:http://dx.doi.org/10.1016/j.juro.2010.12.058

  • Galinsky DST, Nechushtan H (2008) Mast cells and cancer—no longer just basic science. Crit Rev Oncol/Hematol 68(2):115–130. doi:http://dx.doi.org/10.1016/j.critrevonc.2008.06.001

  • Galli SJ (2000) Mast cells and basophils. Curr Opin Hematol 7(1):32–39

    CAS  PubMed  Google Scholar 

  • Galli R, Starace D, Busà R, Angelini DF, Paone A, De Cesaris P, Filippini A, Sette C, Battistini L, Ziparo E, Riccioli A (2010) TLR stimulation of prostate tumor cells induces chemokine-mediated recruitment of specific immune cell types. J Immunol 184(12):6658–6669. doi:10.4049/jimmunol.0902401

    CAS  PubMed  Google Scholar 

  • Gocheva V, Wang H-W, Gadea BB, Shree T, Hunter KE, Garfall AL, Berman T, Joyce JA (2010) IL-4 induces cathepsin protease activity in tumor-associated macrophages to promote cancer growth and invasion. Genes Dev 24(3):241–255. doi:10.1101/gad.1874010

    CAS  PubMed Central  PubMed  Google Scholar 

  • Gonzalez-Reyes S, Fernandez J, Gonzalez L, Aguirre A, Suarez A, Gonzalez J, Escaff S, Vizoso F (2011) Study of TLR3, TLR4, and TLR9 in prostate carcinomas and their association with biochemical recurrence. Cancer Immunol Immunother 60(2):217–226

    CAS  PubMed  Google Scholar 

  • Gooch JL, Lee AV, Yee D (1998) Interleukin 4 inhibits growth and induces apoptosis in human breast cancer cells. Cancer Res 58(18):4199–4205

    CAS  PubMed  Google Scholar 

  • Gordon JR, Galli SJ (1990) Mast cells as a source of both preformed and immunologically inducible TNF-[alpha]/cachectin. Nature 346(6281):274–276

    CAS  PubMed  Google Scholar 

  • Gordon J, Burd P, Galli S (1990) Mast cells as a source of multifunctional cytokines. Immunol Today 11(12):458–464

    CAS  PubMed  Google Scholar 

  • Gounaris E, Erdman SE, Restaino C, Gurish MF, Friend DS, Gounari F, Lee DM, Zhang G, Glickman JN, Shin K, Rao VP, Poutahidis T, Weissleder R, McNagny KM, Khazaie K (2007) Mast cells are an essential hematopoietic component for polyp development. Proc Natl Acad Sci 104(50):19977–19982. doi:10.1073/pnas.0704620104

    CAS  PubMed Central  PubMed  Google Scholar 

  • Grivennikov SI, Wang K, Mucida D, Stewart CA, Schnabl B, Jauch D, Taniguchi K, Yu G-Y, Osterreicher CH, Hung KE, Datz C, Feng Y, Fearon ER, Oukka M, Tessarollo L, Coppola V, Yarovinsky F, Cheroutre H, Eckmann L, Trinchieri G, Karin M (2012) Adenoma-linked barrier defects and microbial products drive IL-23/IL-17-mediated tumour growth. Nature 491(7423):254–258. doi:http://www.nature.com/nature/journal/v491/n7423/abs/nature11465.html#supplementary-information

  • Gruber BL, Kew RR, Jelaska A, Marchese MJ, Garlick J, Ren S, Schwartz LB, Korn JH (1997) Human mast cells activate fibroblasts: tryptase is a fibrogenic factor stimulating collagen messenger ribonucleic acid synthesis and fibroblast chemotaxis. J Immunol 158(5):2310–2317

    CAS  PubMed  Google Scholar 

  • Gui-zhong LI, Libo M, Guanglin H, Jianwei W (2011) The correlation of extent and grade of inflammation with serum PSA levels in patients with IV prostatitis. Int Urol Nephrol 43(2):295–301. doi:10.1007/s11255-010-9825-5

    PubMed  Google Scholar 

  • Gurish MF, Pear WS, Stevens RL, Scott ML, Sokol K, Ghildyal N, Webster MJ, Hu X, Austen KF, Baltimore D, Friend DS (1995) Tissue-regulated differentiation and maturation of a v-abl-immortalized mast cell-committed progenitor. Immunity 3(2):175–186

    CAS  PubMed  Google Scholar 

  • Hagemann T, Balkwill F, Lawrence T (2007) Inflammation and cancer: a double-edged sword. Cancer Cell 12(4):300–301. doi:http://dx.doi.org/10.1016/j.ccr.2007.10.005

  • Hanahan D, Weinberg Robert A (2011) Hallmarks of cancer: the next generation. Cell 144(5):646–674. doi:http://dx.doi.org/10.1016/j.cell.2011.02.013

  • Hao N-B, Lü M-H, Fan Y-H, Cao Y-L, Zhang Z-R, Yang S-M (2012) Macrophages in tumor microenvironments and the progression of tumors. Clin Dev Immunol 2012:11. doi:10.1155/2012/948098

    Google Scholar 

  • Harashima N, Inao T, Imamura R, Okano S, Suda T, Harada M (2012) Roles of the PI3K/Akt pathway and autophagy in TLR3 signaling-induced apoptosis and growth arrest of human prostate cancer cells. Cancer Immunol Immunother 61(5):667–676. doi:10.1007/s00262-011-1132-1

    CAS  PubMed  Google Scholar 

  • Herroon MK, Rajagurubandara E, Rudy DL, Chalasani A, Hardaway AL, Podgorski I (2013) Macrophage cathepsin K promotes prostate tumor progression in bone. Oncogene 32(12):1580–1593. doi:http://www.nature.com/onc/journal/v32/n12/suppinfo/onc2012166s1.html

  • Hobisch A, Rogatsch H, Hittmair A, Fuchs D, Bartsch G, Klocker H, Culig Z (2000) Immunohistochemical localization of interleukin-6 and its receptor in benign, premalignant and malignant prostate tissue. J Pathol 191(3):239–244. doi:10.1002/1096-9896(2000)9999:9999<:aid-path633>3.0.co;2-x

    CAS  PubMed  Google Scholar 

  • Hood BL, Darfler MM, Guiel TG, Furusato B, Lucas DA, Ringeisen BR, Sesterhenn IA, Conrads TP, Veenstra TD, Krizman DB (2005) Proteomic analysis of formalin-fixed prostate cancer tissue. Mol Cell Proteomics 4(11):1741–1753. doi:10.1074/mcp.M500102-MCP200

    CAS  PubMed  Google Scholar 

  • Horner M, Ries L, Krapcho M, Neyman N, Aminou R, Howlader N, Altekruse SF, Feuer EJ, Huang L, Mariotto A, Miller BA, Lewis DR, Eisner MP, Stinchcomb DG, E BK (2009) SEER Cancer Statistics Review, 1975–2006. National Cancer Institute, Bethesda, MD

    Google Scholar 

  • Iamaroon A, Pongsiriwet S, Jittidecharaks S, Pattanaporn K, Prapayasatok S, Wanachantararak S (2003) Increase of mast cells and tumor angiogenesis in oral squamous cell carcinoma. J Oral Pathol Med 32(4):195–199. doi:10.1034/j.1600-0714.2003.00128.x

    PubMed  Google Scholar 

  • Iliopoulos D, Hirsch HA, Wang G, Struhl K (2011) Inducible formation of breast cancer stem cells and their dynamic equilibrium with non-stem cancer cells via IL6 secretion. Proc Natl Acad Sci 108(4):1397–1402. doi:10.1073/pnas.1018898108

    CAS  PubMed Central  PubMed  Google Scholar 

  • Irani AA, Schechter NM, Craig SS, DeBlois G, Schwartz LB (1986) Two types of human mast cells that have distinct neutral protease compositions. Proc Natl Acad Sci 83(12):4464–4468

    CAS  PubMed Central  PubMed  Google Scholar 

  • Irani J, Goujon J-M, Ragni E, Peyrat L, Hubert J, Saint F, Mottet N (1999) High-grade inflammation in prostate cancer as a prognostic factor for biochemical recurrence after radical prostatectomy. Urology 54(3):467–472. doi:http://dx.doi.org/10.1016/S0090-4295(99)00152-1

  • Johansson A, Rudolfsson S, Hammarsten P, Halin S, Pietras K, Jones J, Stattin P, Egevad L, Granfors T, Wikström P, Bergh A (2010) Mast cells are novel independent prognostic markers in prostate cancer and represent a target for therapy. Am J Pathol 177(2):1031–1041. doi:http://dx.doi.org/10.2353/ajpath.2010.100070

  • Kaler P, Godasi B, Augenlicht L, Klampfer L (2009) The NF-kappaB/AKT-dependent Induction of Wnt signaling in colon cancer cells by macrophages and IL-1beta. Cancer Microenviron

    Google Scholar 

  • Kang J-C, Chen J-S, Lee C-H, Chang J-J, Shieh Y-S (2010) Intratumoral macrophage counts correlate with tumor progression in colorectal cancer. J Surg Oncol 102(3):242–248. doi:10.1002/jso.21617

    CAS  PubMed  Google Scholar 

  • Karan D, Holzbeierlein J, Thrasher JB (2009) Macrophage inhibitory cytokine-1: possible bridge molecule of inflammation and prostate cancer. Cancer Res 69(1):2–5. doi:10.1158/0008-5472.can-08-1230

    CAS  PubMed  Google Scholar 

  • Karja V, Aaltomaa S, Lipponen P, Isotalo T, Talja M, Mokka R (2005) Tumour-infiltrating lymphocytes: a prognostic factor of PSA-free survival in patients with local prostate carcinoma treated by radical prostatectomy. Anticancer Res 25(6C):4435–4438

    PubMed  Google Scholar 

  • Kazma R, Mefford JA, Cheng I, Plummer SJ, Levin AM, Rybicki BA, Casey G, Witte JS (2012) Association of the innate immunity and inflammation pathway with advanced prostate cancer risk. PLoS ONE 7(12):e51680. doi:10.1371/journal.pone.0051680

    CAS  PubMed Central  PubMed  Google Scholar 

  • Kennedy R, Celis E (2008) Multiple roles for CD4+ T cells in anti-tumor immune responses. Immunol Rev 222(1):129–144. doi:10.1111/j.1600-065X.2008.00616.x

    CAS  PubMed  Google Scholar 

  • Khazaie K, Blatner N, Khan M, Gounari F, Gounaris E, Dennis K, Bonertz A, Tsai F, Strouch M, Cheon E, Phillips J, Beckhove P, Bentrem D (2011) The significant role of mast cells in cancer. Cancer Metastasis Rev 30(1):45–60

    CAS  PubMed  Google Scholar 

  • Kim H, Bae J, Chang I, Kim K, Lee J, Shin H, Lee J, Kim W-J, Kim W, Myung S (2012) Sequence variants of toll-like receptor 4 (TLR4) and the risk of prostate cancer in Korean men. World J Urol 30(2):225–232. doi:10.1007/s00345-011-0690-3

    CAS  PubMed  Google Scholar 

  • Kimura A, Kishimoto T (2010) IL-6: regulator of Treg/Th17 balance. Eur J Immunol 40(7):1830–1835. doi:10.1002/eji.201040391

    CAS  PubMed  Google Scholar 

  • Kiniwa Y, Miyahara Y, Wang HY, Peng W, Peng G, Wheeler TM, Thompson TC, Old LJ, Wang R-F (2007) CD8+ Foxp3+ regulatory T cells mediate immunosuppression in prostate cancer. Clin Cancer Res 13(23):6947–6958. doi:10.1158/1078-0432.ccr-07-0842

    CAS  PubMed  Google Scholar 

  • Krieger J, Nyberg L, Nickel J (1999) NIH consensus definition and classification of prostatitis. JAMA 282(3):236–237. doi:10-1001/pubs.JAMA-ISSN-0098-7484-282-3-jac90006

    CAS  PubMed  Google Scholar 

  • Krishnaswamy G, Kelley J, Johnson D, Youngberg G, Stone W, Huang S, Bieber J, Chi D (2001) The human mast cell: functions in physiology and disease. Front Biosci 6:D1109–D1127

    CAS  PubMed  Google Scholar 

  • LaBarge MA, Nelson CM, Villadsen R, Fridriksdottir A, Ruth JR, Stampfer MR, Petersen OW, Bissell MJ (2009) Human mammary progenitor cell fate decisions are products of interactions with combinatorial microenvironments. Integr Biol 1(1):70–79

    CAS  Google Scholar 

  • Lacy P, Stow JL (2011) Cytokine release from innate immune cells: association with diverse membrane trafficking pathways. Blood 118(1):9–18. doi:10.1182/blood-2010-08-265892

    CAS  PubMed  Google Scholar 

  • Leavy O (2010) Regulatory T cells: CD8+ TReg cells join the fold. Nat Rev Immunol 10(10):680–681

    CAS  PubMed  Google Scholar 

  • Lee Y-M, Jippo T, Kim D-K, Katsu Y, Tsujino K, Morii E, Kim H-M, Adachi S, Nawa Y, Kitamura Y (1998) Alteration of protease expression phenotype of mouse peritoneal mast cells by changing the microenvironment as demonstrated by in situ hybridization histochemistry. Am J Pathol 153(3):931–936. doi:http://dx.doi.org/10.1016/S0002-9440(10)65634-9

  • Lee SO, Lou W, Hou M, de Miguel F, Gerber L, Gao AC (2003) Interleukin-6 promotes androgen-independent growth in LNCaP human prostate cancer cells. Clin Cancer Res 9(1):370–376

    CAS  PubMed  Google Scholar 

  • Levi-Schaffer F, Piliponsky AM (2003) Tryptase, a novel link between allergic inflammation and fibrosis. Trends Immunol 24(4):158–161. doi:http://dx.doi.org/10.1016/S1471-4906(03)00058-9

  • Li Y-W, Qiu S-J, Fan J, Gao Q, Zhou J, Xiao Y-S, Xu Y, Wang X-Y, Sun J, Huang X-W (2009a) Tumor-infiltrating macrophages can predict favorable prognosis in hepatocellular carcinoma after resection. J Cancer Res Clin Oncol 135(3):439–449. doi:10.1007/s00432-008-0469-0

    PubMed  Google Scholar 

  • Li Y-Y, Hsieh L-L, Tang R-P, Liao S-K, Yeh K-Y (2009b) Interleukin-6 (IL-6) released by macrophages induces IL-6 secretion in the human colon cancer HT-29 cell line. Hum Immunol 70(3):151–158. doi:http://dx.doi.org/10.1016/j.humimm.2009.01.004

  • Lindahl C, Simonsson M, Bergh A, Thysell E, Antti H, Sund M, Wikstrom P (2009) Increased levels of macrophage-secreted cathepsin S during prostate cancer progression in TRAMP mice and patients. Cancer Genomics Proteomics 6(3):149–159

    CAS  PubMed  Google Scholar 

  • Lissbrant I, Stattin P, Wikstrom P, Damber J, Egevad L, Bergh A (2000) Tumor associated macrophages in human prostate cancer: relation to clinicopathological variables and survival. Int J Oncol 17(3):445–451

    CAS  PubMed  Google Scholar 

  • Liu T, Bauskin AR, Zaunders J, Brown DA, Pankurst S, Russell PJ, Breit SN (2003) Macrophage inhibitory cytokine 1 reduces cell adhesion and induces apoptosis in prostate cancer cells. Cancer Res 63(16):5034–5040

    CAS  PubMed  Google Scholar 

  • Liu S, Lachapelle J, Leung S, Gao D, Foulkes W, Nielsen T (2012) CD8+ lymphocyte infiltration is an independent favorable prognostic indicator in basal-like breast cancer. Breast Cancer Res 14(2):R48

    CAS  PubMed Central  PubMed  Google Scholar 

  • Loberg RD, Day LL, Harwood J, Ying C, St John LN, Giles R, Neeley CK, Pienta KJ (2006) CCL2 (Monocyte chemoattractant protein-1) is a potent regulator of prostate cancer cell migration and proliferation. Neoplasia 8(7):578–586

    CAS  PubMed Central  PubMed  Google Scholar 

  • Lucia M, Lambert J, Platz EA, De Marzo AM (2010) Inflammation as a target in prostate cancer. In: Figg WD, Chau CH, Small EJ (eds) Drug management of prostate cancer. Springer, New York, NY, pp 375–386

    Google Scholar 

  • Malinowska K, Neuwirt H, Cavarretta IT, Bektic J, Steiner H, Dietrich H, Moser PL, Fuchs D, Hobisch A, Culig Z (2009) Interleukin-6 stimulation of growth of prostate cancer in vitro and in vivo through activation of the androgen receptor. Endocr Relat Cancer 16(1):155–169. doi:10.1677/erc-08-0174

    CAS  PubMed  Google Scholar 

  • Maltby S, Khazaie K, McNagny KM (2009) Mast cells in tumor growth: angiogenesis, tissue remodelling and immune-modulation. Biochimica et Biophysica Acta (BBA) Rev Cancer 1796(1):19–26. doi:http://dx.doi.org/10.1016/j.bbcan.2009.02.001

  • Martin F, Apetoh L, Ghiringhelli F (2012) Controversies on the role of Th17 in cancer: a TGF-β-dependent immunosuppressive activity? Trends Mol Med 18(12):742–749

    CAS  PubMed  Google Scholar 

  • McArdle PA, Canna K, McMillan DC, McNicol AM, Campbell R, Underwood MA (2004) The relationship between T-lymphocyte subset infiltration and survival in patients with prostate cancer. Br J Cancer 91(3):541–543

    CAS  PubMed Central  PubMed  Google Scholar 

  • Miller AM, Lundberg K, Özenci V, Banham AH, Hellström M, Egevad L, Pisa P (2006) CD4+CD25high T cells are enriched in the tumor and peripheral blood of prostate cancer patients. J Immunol 177(10):7398–7405

    CAS  PubMed  Google Scholar 

  • Mizutani K, Sud S, McGregor N, Martinovski G, Rice B, Craig M, Varsos Z, Roca H, Pienta K (2009) The chemokine CCL2 increases prostate tumor growth and bone metastasis through macrophage and osteoclast recruitment. Neoplasia 11(11):1235–1242

    CAS  PubMed Central  PubMed  Google Scholar 

  • Molin D (2004) Bystander cells and prognosis in Hodgkin lymphoma. Review based on a doctoral thesis. Ups J Med Sci 109(3):179–228

    PubMed  Google Scholar 

  • Molin D, Edström A, Glimelius I, Glimelius B, Nilsson G, Sundström C, Enblad G (2002) Mast cell infiltration correlates with poor prognosis in Hodgkin’s lymphoma. Br J Haematol 119(1):122–124. doi:10.1046/j.1365-2141.2002.03768.x

    PubMed  Google Scholar 

  • Mougiakakos D, Choudhury A, Lladser A, Kiessling R, Johansson CC (2010) Regulatory T cells in cancer. In: George FVW, George K (eds) Advances in cancer research, vol 107. Academic Press, pp 57–117. doi:http://dx.doi.org/10.1016/S0065-230X(10)07003-X

  • Naito Y, Saito K, Shiiba K, Ohuchi A, Saigenji K, Nagura H, Ohtani H (1998) CD8+ T cells infiltrated within cancer cell nests as a prognostic factor in human colorectal cancer. Cancer Res 58(16):3491–3494

    CAS  PubMed  Google Scholar 

  • Nakamura T, Scorilas A, Stephan C, Yousef GM, Kristiansen G, Jung K, Diamandis EP (2003) Quantitative analysis of macrophage inhibitory cytokine-1 (MIC-1) gene expression in human prostatic tissues. Br J Cancer 88(7):1101–1104

    CAS  PubMed Central  PubMed  Google Scholar 

  • Nakayama M, Bennett CJ, Hicks JL, Epstein JI, Platz EA, Nelson WG, De Marzo AM (2003) Hypermethylation of the human glutathione S-transferase-π gene (GSTP1) CpG island is present in a subset of proliferative inflammatory atrophy lesions but not in normal or hyperplastic epithelium of the prostate: a detailed study using laser-capture microdissection. Am J Pathol 163(3):923–933. doi:http://dx.doi.org/10.1016/S0002-9440(10)63452-9

  • Nakayama T, Yao L, Tosato G (2004) Mast cell-derived angiopoietin-1 plays a critical role in the growth of plasma cell tumors. J Clin Investig 114(9):1317–1325. doi:10.1172/jci22089

    CAS  PubMed Central  PubMed  Google Scholar 

  • Nelson WG, De Marzo AM, Isaacs WB (2003) Prostate cancer. N Engl J Med 349(4):366–381. doi:10.1056/NEJMra021562

    CAS  PubMed  Google Scholar 

  • Nelson W, Sfanos K, DeMarzo A, Yegnasubramanian S (2013) Prostate inflammation and prostate cancer. In: Klein EA, Jones JS (eds) Management of prostate cancer, current clinical urology. Humana Press, New York, NY, pp 103–115

    Google Scholar 

  • Nickel JC, Downey J, Young I, Boag S (1999) Asymptomatic inflammation and/or infection in benign prostatic hyperplasia. BJU International 84(9):976–981. doi:10.1046/j.1464-410x.1999.00352.x

  • Nonomura N, Takayama H, Nishimura K, Oka D, Nakai Y, Shiba M, Tsujimura A, Nakayama M, Aozasa K, Okuyama A (2007) Decreased number of mast cells infiltrating into needle biopsy specimens leads to a better prognosis of prostate cancer. Br J Cancer 97(7):952–956

    CAS  PubMed Central  PubMed  Google Scholar 

  • Nonomura N, Takayama H, Nakayama M, Nakai Y, Kawashima A, Mukai M, Nagahara A, Aozasa K, Tsujimura A (2011) Infiltration of tumour-associated macrophages in prostate biopsy specimens is predictive of disease progression after hormonal therapy for prostate cancer. BJU Int 107(12):1918–1922. doi:10.1111/j.1464-410X.2010.09804.x

    PubMed  Google Scholar 

  • Okamoto M, Lee C, Oyasu R (1997) Interleukin-6 as a paracrine and autocrine growth factor in human prostatic carcinoma cells in vitro. Cancer Res 57(1):141–146

    CAS  PubMed  Google Scholar 

  • Ostrand-Rosenberg S, Sinha P (2009) Myeloid-derived suppressor cells: linking inflammation and cancer. J Immunol 182(8):4499–4506. doi:10.4049/jimmunol.0802740

    CAS  PubMed Central  PubMed  Google Scholar 

  • Palapattu GS, Sutcliffe S, Bastian PJ, Platz EA, De Marzo AM, Isaacs WB, Nelson WG (2005) Prostate carcinogenesis and inflammation: emerging insights. Carcinogenesis 26(7):1170–1181. doi:10.1093/carcin/bgh317

    CAS  PubMed  Google Scholar 

  • Paone A, Starace D, Galli R, Padula F, De Cesaris P, Filippini A, Ziparo E, Riccioli A (2008) Toll-like receptor 3 triggers apoptosis of human prostate cancer cells through a PKC-α-dependent mechanism. Carcinogenesis 29(7):1334–1342. doi:10.1093/carcin/bgn149

    CAS  PubMed  Google Scholar 

  • Pardoll D (2002) T cells take aim at cancer. Proc Natl Acad Sci 99(25):15840–15842. doi:10.1073/pnas.262669499

    CAS  PubMed Central  PubMed  Google Scholar 

  • Pittoni P, Colombo MP (2012) The dark side of mast cell-targeted therapy in prostate cancer. Cancer Res 72(4):831–835. doi:10.1158/0008-5472.can-11-3110

    CAS  PubMed  Google Scholar 

  • Pittoni P, Tripodo C, Piconese S, Mauri G, Parenza M, Rigoni A, Sangaletti S, Colombo MP (2011) Mast cell targeting hampers prostate adenocarcinoma development but promotes the occurrence of highly malignant neuroendocrine cancers. Cancer Res. doi:10.1158/0008-5472.can-11-1637

    PubMed  Google Scholar 

  • Platz EA, De Marzo AM, Erlinger TP, Rifai N, Visvanathan K, Hoffman SC, Helzlsouer KJ (2004) No association between pre-diagnostic plasma C-reactive protein concentration and subsequent prostate cancer. Prostate 59(4):393–400. doi:10.1002/pros.10368

    CAS  PubMed  Google Scholar 

  • Ports MO, Nagle RB, Pond GD, Cress AE (2009) Extracellular engagement of α6 integrin inhibited urokinase-type plasminogen activator-mediated cleavage and delayed human prostate bone metastasis. Cancer Res 69(12):5007–5014. doi:10.1158/0008-5472.can-09-0354

    CAS  PubMed Central  PubMed  Google Scholar 

  • Powell IJ, Dyson G, Land S, Ruterbusch J, Bock CH, Lenk S, Herawi M, Everson RB, Giroux CN, Schwartz AG, Bollig-Fischer A (2013) Genes associated with prostate cancer are differentially expressed in African American and European American men. Cancer Epidemiol Biomark Prev. doi:10.1158/1055-9965.epi-12-1238

    Google Scholar 

  • Proctor MJ, Talwar D, Balmar SM, O’Reilly DSJ, Foulis AK, Horgan PG, Morrison DS, McMillan DC (2010) The relationship between the presence and site of cancer, an inflammation-based prognostic score and biochemical parameters. Initial results of the Glasgow inflammation outcome study. Br J Cancer 103(6):870–876

    CAS  PubMed Central  PubMed  Google Scholar 

  • Punturieri A, Filippov S, Allen E, Caras I, Murray R, Reddy V, Weiss SJ (2000) Regulation of elastinolytic cysteine proteinase activity in normal and cathepsin K–deficient human macrophages. J Exp Med 192(6):789–800. doi:10.1084/jem.192.6.789

    CAS  PubMed Central  PubMed  Google Scholar 

  • Putzi MJ, De Marzo AM (2000) Morphologic transitions between proliferative inflammatory atrophy and high-grade prostatic intraepithelial neoplasia. Urology 56(5):828–832. doi:http://dx.doi.org/10.1016/S0090-4295(00)00776-7

  • Rajput A, Turbin D, Cheang M, Voduc D, Leung S, Gelmon K, Gilks CB, Huntsman D (2008) Stromal mast cells in invasive breast cancer are a marker of favourable prognosis: a study of 4,444 cases. Breast Cancer Res Treat 107(2):249–257. doi:10.1007/s10549-007-9546-3

    PubMed Central  PubMed  Google Scholar 

  • Rakoff-Nahoum S, Medzhitov R (2009) Toll-like receptors and cancer. Nat Rev Cancer 9(1):57–63

    CAS  PubMed  Google Scholar 

  • Rao UNM, Lee SJ, Luo W, Mihm MC, Kirkwood JM (2010) Presence of tumor-infiltrating lymphocytes and a dominant nodule within primary melanoma are prognostic factors for relapse-free survival of patients with thick (T4) primary melanoma: pathologic analysis of the E1690 and E1694 intergroup trials. Am J Clin Pathol 133(4):646–653. doi:10.1309/ajcptxmefovywda6

    PubMed Central  PubMed  Google Scholar 

  • Rasiah KK, Kench JG, Gardiner-Garden M, Biankin AV, Golovsky D, Brenner PC, Kooner R, O’Neill GF, Turner JJ, Delprado W, Lee CS, Brown DA, Breit SN, Grygiel JJ, Horvath LG, Stricker PD, Sutherland RL, Henshall SM (2006) Aberrant neuropeptide Y and macrophage inhibitory cytokine-1 expression are early events in prostate cancer development and are associated with poor prognosis. Cancer Epidemiol Biomark Prev 15(4):711–716. doi:10.1158/1055-9965.epi-05-0752

    CAS  Google Scholar 

  • Reams RR, Agrawal D, Davis M, Yoder S, Odedina F, Kumar N, Higginbotham J, Akinremi T, Suther S, Soliman K (2009) Microarray comparison of prostate tumor gene expression in African-American and Caucasian American males: a pilot project study. Infect Agents Cancer 4(Suppl 1):S3

    PubMed Central  PubMed  Google Scholar 

  • Ribatti D, Vacca A, Nico B, Quondamatteo F, Ria R, Minischetti M, Marzullo A, Herken R, Roncali L, Dammacco F (1999) Bone marrow angiogenesis and mast cell density increase simultaneously with progression of human multiple myeloma. Br J Cancer 79(3–4):451–455

    CAS  PubMed Central  PubMed  Google Scholar 

  • Ribatti D, Vacca A, Ria R, Marzullo A, Nico B, Filotico R, Roncali L, Dammacco F (2003) Neovascularisation, expression of fibroblast growth factor-2, and mast cells with tryptase activity increase simultaneously with pathological progression in human malignant melanoma. Eur J Cancer 39(5):666–674. doi:http://dx.doi.org/10.1016/S0959-8049(02)00150-8

  • Ribatti D, Finato N, Crivellato E, Marzullo A, Mangieri D, Nico B, Vacca A, Beltrami CA (2005) Neovascularization and mast cells with tryptase activity increase simultaneously with pathologic progression in human endometrial cancer. Am J Obstet Gynecol 193(6):1961–1965. doi:http://dx.doi.org/10.1016/j.ajog.2005.04.055

  • Richardsen E, Uglehus RD, Due J, Busch C, Busund LTR (2008) The prognostic impact of M-CSF, CSF-1 receptor, CD68 and CD3 in prostatic carcinoma. Histopathology 53(1):30–38. doi:10.1111/j.1365-2559.2008.03058.x

    CAS  PubMed  Google Scholar 

  • Rigamonti N, Capuano G, Ricupito A, Jachetti E, Grioni M, Generoso L, Freschi M, Bellone M (2011) Modulators of arginine metabolism do not impact on peripheral T-cell tolerance and disease progression in a model of spontaneous prostate cancer. Clin Cancer Res 17(5):1012–1023. doi:10.1158/1078-0432.ccr-10-2547

    CAS  PubMed  Google Scholar 

  • Roca H, Varsos ZS, Sud S, Craig MJ, Ying C, Pienta KJ (2009) CCL2 and interleukin-6 promote survival of human CD11b+ peripheral blood mononuclear cells and induce M2-type macrophage polarization. J Biol Chem 284(49):34342–34354. doi:10.1074/jbc.M109.042671

    CAS  PubMed Central  PubMed  Google Scholar 

  • Sari S, Çandir Ö, Öztürk K (1999) Mast cell variations in tumour tissue and with histopathological grading in specimens of prostatic adenocarcinoma. BJU Int 84(7):851–853. doi:10.1046/j.1464-410x.1999.00245.x

    CAS  PubMed  Google Scholar 

  • Schumacher K, Haensch W, Röefzaad C, Schlag PM (2001) Prognostic significance of activated CD8+ T cell infiltrations within esophageal carcinomas. Cancer Res 61(10):3932–3936

    CAS  PubMed  Google Scholar 

  • Selander KS, Brown DA, Sequeiros GB, Hunter M, Desmond R, Parpala T, Risteli J, Breit SN, Jukkola-Vuorinen A (2007) Serum macrophage inhibitory cytokine-1 concentrations correlate with the presence of prostate cancer bone metastases. Cancer Epidemiol Biomark Prev 16(3):532–537. doi:10.1158/1055-9965.epi-06-0841

    CAS  Google Scholar 

  • Sfanos KS, De Marzo AM (2012) Prostate cancer and inflammation: the evidence. Histopathology 60(1):199–215. doi:10.1111/j.1365-2559.2011.04033.x

    PubMed Central  PubMed  Google Scholar 

  • Sfanos KS, Bruno TC, Maris CH, Xu L, Thoburn CJ, DeMarzo AM, Meeker AK, Isaacs WB, Drake CG (2008) Phenotypic analysis of prostate-infiltrating lymphocytes reveals TH17 and Treg skewing. Clin Cancer Res 14(11):3254–3261. doi:10.1158/1078-0432.ccr-07-5164

    CAS  PubMed Central  PubMed  Google Scholar 

  • Sfanos KS, Bruno TC, Meeker AK, De Marzo AM, Isaacs WB, Drake CG (2009a) Human prostate-infiltrating CD8+ T lymphocytes are oligoclonal and PD-1+. Prostate 69(15):1694–1703. doi:10.1002/pros.21020

    CAS  PubMed Central  PubMed  Google Scholar 

  • Sfanos KS, Wilson BA, De Marzo AM, Isaacs WB (2009b) Acute inflammatory proteins constitute the organic matrix of prostatic corpora amylacea and calculi in men with prostate cancer. Proc Natl Acad Sci 106(9):3443–3448. doi:10.1073/pnas.0810473106

    CAS  PubMed Central  PubMed  Google Scholar 

  • Shafique K, Proctor MJ, McMillan DC, Qureshi K, Leung H, Morrison DS (2012) Systemic inflammation and survival of patients with prostate cancer: evidence from the Glasgow inflammation outcome study. Prostate Cancer Prostatic Dis 15(2):195–201

    CAS  PubMed  Google Scholar 

  • Shimura S, Yang G, Ebara S, Wheeler TM, Frolov A, Thompson TC (2000) Reduced infiltration of tumor-associated macrophages in human prostate cancer: association with cancer progression. Cancer Res 60(20):5857–5861

    CAS  PubMed  Google Scholar 

  • Shui IM, Stark JR, Penney KL, Schumacher FR, Epstein MM, Pitt MJ, Stampfer MJ, Tamimi RM, Lindstrom S, Sesso HD, Fall K, Ma J, Kraft P, Giovannucci E, Mucci LA (2012) Genetic variation in the toll-like receptor 4 and prostate cancer incidence and mortality. Prostate 72(2):209–216. doi:10.1002/pros.21423

    CAS  PubMed Central  PubMed  Google Scholar 

  • Smith PC, Hobisch A, Lin D-L, Culig Z, Keller ET (2001) Interleukin-6 and prostate cancer progression. Cytokine Growth Factor Rev 12(1):33–40. doi:http://dx.doi.org/10.1016/S1359-6101(00)00021-6

  • Sroka IC, Sandoval CP, Chopra H, Gard JMC, Pawar SC, Cress AE (2011) Macrophage-dependent cleavage of the laminin receptor α6β1 in prostate cancer. Mol Cancer Res 9(10):1319–1328. doi:10.1158/1541-7786.mcr-11-0080

    CAS  PubMed Central  PubMed  Google Scholar 

  • Stimac G, Reljic A, Spajic B, Dimanovski J, Ruzic B, Ulamec M, Sonicki Z, Kraus O (2009) Aggressiveness of inflammation in histological prostatitis-correlation with total and free prostate specific antigen levels in men with biochemical criteria for prostate biopsy. Scott Med J 54(3):8–12. doi:10.1258/rsmsmj.54.3.8

    CAS  PubMed  Google Scholar 

  • Strouch MJ, Cheon EC, Salabat MR, Krantz SB, Gounaris E, Melstrom LG, Dangi-Garimella S, Wang E, Munshi HG, Khazaie K, Bentrem DJ (2010) Crosstalk between mast cells and pancreatic cancer cells contributes to pancreatic tumor progression. Clin Cancer Res 16(8):2257–2265. doi:10.1158/1078-0432.ccr-09-1230

    CAS  PubMed Central  PubMed  Google Scholar 

  • Sun J, Wiklund F, Zheng SL, Chang B, Bälter K, Li L, Johansson J-E, Li G, Adami H-O, Liu W, Tolin A, Turner AR, Meyers DA, Isaacs WB, Xu J, Grönberg H (2005) Sequence variants in toll-like receptor gene cluster (TLR6-TLR1-TLR10) and prostate cancer risk. J Natl Cancer Inst 97(7):525–532. doi:10.1093/jnci/dji070

    CAS  PubMed  Google Scholar 

  • Svensson RU, Haverkamp JM, Thedens DR, Cohen MB, Ratliff TL, Henry MD (2011) Slow disease progression in a C57BL/6 Pten-deficient mouse model of prostate cancer. Am J Pathol 179(1):502–512. doi:http://dx.doi.org/10.1016/j.ajpath.2011.03.014

  • Swann JB, Smyth MJ (2007) Immune surveillance of tumors. J Clin Investig 117(5):1137–1146. doi:10.1172/jci31405

    CAS  PubMed Central  PubMed  Google Scholar 

  • Tanner J, Tosato G (1992) Regulation of B-cell growth and immunoglobulin gene transcription by interleukin-6. Blood 79(2):452–459

    CAS  PubMed  Google Scholar 

  • Theoharides TC, Conti P (2004) Mast cells: the JEKYLL and HYDE of tumor growth. Trends Immunol 25(5):235–241. doi:http://dx.doi.org/10.1016/j.it.2004.02.013

  • Tuna B, Yorukoglu K, Unlu M, Mungan MU, Kirkali Z (2006) Association of mast cells with microvessel density in renal cell carcinomas. European Urol 50(3):530–534. doi:http://dx.doi.org/10.1016/j.eururo.2005.12.040

  • Turnis ME, Korman AJ, Drake CG, Vignali DAA (2012) Combinatorial immunotherapy: PD-1 may not be LAG-ing behind any more. OncoImmunology 1(7):1172–1174

    PubMed Central  PubMed  Google Scholar 

  • Twillie DA, Eisenberger MA, Carducci MA, Hseih W-S, Kim WY, Simons JW (1995) Interleukin-6: a candidate mediator of human prostate cancer morbidity. Urology 45(3):542–549. doi:http://dx.doi.org/10.1016/S0090-4295(99)80034-X

  • Ugurlu O, Yaris M, Oztekin CV, Kosan TM, Adsan O, Cetinkaya M (2010) Impacts of antibiotic and anti-inflammatory therapies on serum prostate-specific antigen levels in the presence of prostatic inflammation: a prospective randomized controlled trial. Urol Int 84(2):185–190. doi:10.1159/000277596

    PubMed  Google Scholar 

  • van Dijk M, Göransson SA, Strömblad S (2013) Cell to extracellular matrix interactions and their reciprocal nature in cancer. Exp Cell Res (0). doi:http://dx.doi.org/10.1016/j.yexcr.2013.02.006

  • Vasiljeva O, Papazoglou A, Krüger A, Brodoefel H, Korovin M, Deussing J, Augustin N, Nielsen BS, Almholt K, Bogyo M, Peters C, Reinheckel T (2006) Tumor cell-derived and macrophage-derived cathepsin B promotes progression and lung metastasis of mammary cancer. Cancer Res 66(10):5242–5250. doi:10.1158/0008-5472.can-05-4463

    CAS  PubMed  Google Scholar 

  • Vesalainen S, Lipponen P, Talja M, Syrjänen K (1994) Histological grade, perineural infiltration, tumour-infiltrating lymphocytes and apoptosis as determinants of long-term prognosis in prostatic adenocarcinoma. European J Cancer 30(12):1797–1803. doi:http://dx.doi.org/10.1016/0959-8049(94)E0159-2

  • Vesely MD, Kershaw MH, Schreiber RD, Smyth MJ (2011) Natural innate and adaptive immunity to cancer. Annu Rev Immunol 29(1):235–271. doi:10.1146/annurev-immunol-031210-101324

    CAS  PubMed  Google Scholar 

  • Vogelstein B, Papadopoulos N, Velculescu VE, Zhou S, Diaz LA, Kinzler KW (2013) Cancer genome landscapes. Science 339(6127):1546–1558. doi:10.1126/science.1235122

    CAS  PubMed Central  PubMed  Google Scholar 

  • Vykhovanets E, Maclennan G, Vykhovanets O, Gupta S (2011) IL-17 Expression by macrophages is associated with proliferative inflammatory atrophy lesions in prostate cancer patients. Int J Clin Exp Pathol 4(6):552–565

    CAS  PubMed Central  PubMed  Google Scholar 

  • Wallace TA, Prueitt RL, Yi M, Howe TM, Gillespie JW, Yfantis HG, Stephens RM, Caporaso NE, Loffredo CA, Ambs S (2008) Tumor immunobiological differences in prostate cancer between African–American and European–American men. Cancer Res 68(3):927–936. doi:10.1158/0008-5472.can-07-2608

    CAS  PubMed  Google Scholar 

  • Wang W, Bergh A, Damber J-E (2005) Cyclooxygenase-2 expression correlates with local chronic inflammation and tumor neovascularization in human prostate cancer. Clin Cancer Res 11(9):3250–3256. doi:10.1158/1078-0432.ccr-04-2405

    CAS  PubMed  Google Scholar 

  • Wang W, Bergh A, Damber J-E (2009) Morphological transition of proliferative inflammatory atrophy to high-grade intraepithelial neoplasia and cancer in human prostate. Prostate 69(13):1378–1386. doi:10.1002/pros.20992

    PubMed  Google Scholar 

  • Welsh JB, Sapinoso LM, Su AI, Kern SG, Wang-Rodriguez J, Moskaluk CA, Frierson HF, Hampton GM (2001) Analysis of gene expression identifies candidate markers and pharmacological targets in prostate cancer. Cancer Res 61(16):5974–5978

    CAS  PubMed  Google Scholar 

  • Welsh JB, Sapinoso LM, Kern SG, Brown DA, Liu T, Bauskin AR, Ward RL, Hawkins NJ, Quinn DI, Russell PJ, Sutherland RL, Breit SN, Moskaluk CA, Frierson HF, Hampton GM (2003) Large-scale delineation of secreted protein biomarkers overexpressed in cancer tissue and serum. Proc Natl Acad Sci 100(6):3410–3415. doi:10.1073/pnas.0530278100

    CAS  PubMed Central  PubMed  Google Scholar 

  • Welsh TJ, Green RH, Richardson D, Waller DA, O’Byrne KJ, Bradding P (2005) Macrophage and mast-cell invasion of tumor cell islets confers a marked survival advantage in non-small-cell lung cancer. J Clin Oncol 23(35):8959–8967. doi:10.1200/jco.2005.01.4910

    PubMed  Google Scholar 

  • Wiklund FE, Bennet AM, Magnusson PKE, Eriksson UK, Lindmark F, Wu L, Yaghoutyfam N, Marquis CP, Stattin P, Pedersen NL, Adami H-O, Grönberg H, Breit SN, Brown DA (2010) Macrophage inhibitory cytokine-1 (MIC-1/GDF15): a new marker of all-cause mortality. Aging Cell 9(6):1057–1064. doi:10.1111/j.1474-9726.2010.00629.x

    CAS  PubMed  Google Scholar 

  • Wilke CM, Kryczek I, Wei S, Zhao E, Wu K, Wang G, Zou W (2011) Th17 cells in cancer: help or hindrance? Carcinogenesis 32(5):643–649. doi:10.1093/carcin/bgr019

    CAS  PubMed Central  PubMed  Google Scholar 

  • Wu C-T, Hsieh C-C, Lin C-C, Chen W-C, Hong J-H, Chen M-F (2012) Significance of IL-6 in the transition of hormone-resistant prostate cancer and the induction of myeloid-derived suppressor cells. J Mol Med 90(11):1343–1355. doi:10.1007/s00109-012-0916-x

    CAS  PubMed  Google Scholar 

  • Yang G, Addai J, W-h Tian, Frolov A, Wheeler TM, Thompson TC (2004) Reduced infiltration of class A scavenger receptor positive antigen-presenting cells is associated with prostate cancer progression. Cancer Res 64(6):2076–2082. doi:10.1158/0008-5472.can-03-4072

    CAS  PubMed  Google Scholar 

  • Yokokawa J, Cereda V, Remondo C, Gulley JL, Arlen PM, Schlom J, Tsang KY (2008) Enhanced functionality of CD4+CD25highFoxP3+ regulatory T cells in the peripheral blood of patients with prostate cancer. Clin Cancer Res 14(4):1032–1040. doi:10.1158/1078-0432.ccr-07-2056

    CAS  PubMed  Google Scholar 

  • Yoshii M, Jikuhara A, Mori S, Iwagaki H, Takahashi HK, Nishibori M, Tanaka N (2005) Mast cell tryptase stimulates DLD-1 carcinoma through prostaglandin- and MAP kinase-dependent manners. J Pharmacol Sci 98(4):450–458

    CAS  PubMed  Google Scholar 

  • Zhang L, Conejo-Garcia JR, Katsaros D, Gimotty PA, Massobrio M, Regnani G, Makrigiannakis A, Gray H, Schlienger K, Liebman MN, Rubin SC, Coukos G (2003) Intratumoral T cells, recurrence, and survival in epithelial ovarian cancer. N Engl J Med 348(3):203–213. doi:10.1056/NEJMoa020177

    CAS  PubMed  Google Scholar 

  • Zhang B, Rong G, Wei H, Zhang M, Bi J, Ma L, Xue X, Wei G, Liu X, Fang G (2008) The prevalence of Th17 cells in patients with gastric cancer. Biochem Biophys Res Commun 374(3):533–537. doi:http://dx.doi.org/10.1016/j.bbrc.2008.07.060

  • Zhang Q-w, Liu L, Gong C-Y, Shi H-S, Zeng Y-H, Wang X-Z, Zhao Y-W, Wei Y-Q (2012) Prognostic significance of tumor-associated macrophages in solid tumor: a meta-analysis of the literature. PLoS ONE 7(12):e50946. doi:10.1371/journal.pone.0050946

    CAS  PubMed Central  PubMed  Google Scholar 

  • Zheng SL, Augustsson-Bälter K, Chang B, Hedelin M, Li L, Adami H-O, Bensen J, Li G, Johnasson J-E, Turner AR, Adams TS, Meyers DA, Isaacs WB, Xu J, Grönberg H (2004) Sequence variants of toll-like receptor 4 are associated with prostate cancer risk: results from the cancer prostate in Sweden Study. Cancer Res 64(8):2918–2922. doi:10.1158/0008-5472.can-03-3280

    CAS  PubMed  Google Scholar 

  • Zhou Q, Peng R-Q, Wu X-J, Xia Q, Hou J-H, Ding Y, Zhou Q-M, Zhang X, Pang Z-Z, Wan D-S, Zeng Y-X, Zhang X-S (2010) The density of macrophages in the invasive front is inversely correlated to liver metastasis in colon cancer. J Transl Med 8(1):13

    PubMed Central  PubMed  Google Scholar 

  • Zou W, Restifo NP (2010) TH17 cells in tumour immunity and immunotherapy. Nat Rev Immunol 10(4):248–256

    CAS  PubMed Central  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Angelo M. De Marzo .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer Basel

About this chapter

Cite this chapter

Sfanos, K.S., Hempel, H.A., De Marzo, A.M. (2014). The Role of Inflammation in Prostate Cancer. In: Aggarwal, B., Sung, B., Gupta, S. (eds) Inflammation and Cancer. Advances in Experimental Medicine and Biology, vol 816. Springer, Basel. https://doi.org/10.1007/978-3-0348-0837-8_7

Download citation

Publish with us

Policies and ethics