Skip to main content
SpringerLink
Log in

Immunomodulation and Genomic Instability

  • Chapter
  • First Online:
Book cover Genomic Instability and Cancer Metastasis

Part of the book series: Cancer Metastasis - Biology and Treatment ((CMBT,volume 20))

  • 1257 Accesses

Abstract

The interaction between a developing tumor and the immune system is complex and dynamic, and comprises seemingly opposing activities. On one hand, the tumor-promoting effect of chronic inflammation has long been recognized and mechanisms contributing to this activity, including proliferative and anti-apoptotic signaling, tissue remodeling, and mutagenesis, are well described. In contrast, tumor-specific immune responses mediated by a variety of cell types and soluble factors have been shown to inhibit the progression of cancer. A full understanding of the interplay between these opposing forces will be required before clinical manipulation of the tumor immune environment can achieve consistent improvement in the outcomes for patients with cancer. The focus of this chapter is the influence of genomic instability on the pro- and anti-tumor immune activities that impact on cancer development at multiple stages of progression.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
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

Abbreviations

AID:

Activation-induced cytidine deaminase

BER:

Base excision repair

CIN:

Chromosomal instability

DAMP:

Damage-associated molecular patterns

DC:

Dendritic cells

DDR:

DNA damage response

DNA:

Deoxyribonucleic acid

Ig:

Immunoglobulin

KIR:

Killer-cell immunoglobulin-like receptors

M1:

Type 1 macrophages

MDSC:

Myeloid derived suppressor cells

MHC:

Major histocompatibility complex

MIF:

Migration inhibitory factor

MMR:

Mismatch repair

MSI:

Microsatellite instability

MSI-H:

High microsatellite instability

NK:

Natural killer

TLR:

Toll-like receptor

PAMP:

Pathogen-associated molecular patterns

RONS:

Reactive oxygen and nitrogen species

ROS:

Reactive oxygen species

TAMS:

Tumor-associated macrophages

Tfh:

T follicular helper

TREGS :

Regulatory T cells

References

  1. Virchow RLK (1863) Cellular pathology as based upon physiological and pathological histology…/by Rudolf Virchow. Translated from the 2d ed. of the original by Frank Chance. With notes and numerous emendations, principally from MS. notes of the author. 1–562

    Google Scholar 

  2. Mantovani A, Allavena P, Sica A, Balkwill F (2008) Cancer-related inflammation. Nature 454:436–444

    CAS  PubMed  Google Scholar 

  3. Ehrlich P (1909) Über den jetzigen stand der karzinomforschung. Ned Tijdschr Geneeskd 5:273–290

    Google Scholar 

  4. Burnet M (1957) Cancer: a biological approach. III. Viruses associated with neoplastic conditions. IV. Practical applications. Br Med J 1:841–847

    CAS  PubMed Central  PubMed  Google Scholar 

  5. Dunn GP, Bruce AT, Ikeda H, Old LJ, Schreiber RD (2002) Cancer immunoediting: from immunosurveillance to tumor escape. Nat Immunol 3:991–998

    CAS  PubMed  Google Scholar 

  6. Mittal D, Gubin MM, Schreiber RD, Smyth MJ (2014) New insights into cancer immunoediting and its three component phases–elimination, equilibrium and escape. Curr Opin Immunol 27:16–25

    CAS  PubMed  Google Scholar 

  7. Galon J, Costes A, Sanchez-Cabo F et al (2006) Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Science 313:1960–1964

    CAS  PubMed  Google Scholar 

  8. Galon J, Pagès F, Marincola FM et al (2012) Cancer classification using the Immunoscore: a worldwide task force. J Transl Med 10:205

    PubMed Central  PubMed  Google Scholar 

  9. Pagès F, Kirilovsky A, Mlecnik B et al (2009) In situ cytotoxic and memory T cells predict outcome in patients with early-stage colorectal cancer. J Clin Oncol 27:5944–5951

    PubMed  Google Scholar 

  10. Adams S, Gray RJ, Demaria S et al (2014) Prognostic value of tumor-infiltrating lymphocytes in triple-negative breast cancers from two phase III randomized adjuvant breast cancer trials: ECOG 2197 and ECOG 1199. J Clin Oncol. doi: 10.1200/JCO.2013.55.0491

    Google Scholar 

  11. Khan H, Pillarisetty VG, Katz SC (2014) The prognostic value of liver tumor T cell infiltrates. J Surg Res. doi: 10.1016/j.jss.2014.06.001

    Google Scholar 

  12. Schatton T, Scolyer RA, Thompson JF, Mihm MC (2014) Tumor-infiltrating lymphocytes and their significance in melanoma prognosis. Methods Mol Biol 1102:287–324

    PubMed  Google Scholar 

  13. Webb JR, Milne K, Nelson BH (2014) Location, location, location: CD103 demarcates intraepithelial, prognostically favorable CD8(+) tumor-infiltrating lymphocytes in ovarian cancer. Oncoimmunology 3:e27668

    PubMed Central  PubMed  Google Scholar 

  14. Bindea G, Mlecnik B, Tosolini M et al (2013) Spatiotemporal dynamics of intratumoral immune cells reveal the immune landscape in human cancer. Immunity 39:782–795

    CAS  PubMed  Google Scholar 

  15. Colotta F, Allavena P, Sica A, Garlanda C, Mantovani A (2009) Cancer-related inflammation, the seventh hallmark of cancer: links to genetic instability. Carcinogenesis 30:1073–1081

    CAS  PubMed  Google Scholar 

  16. Sun B, Karin M (2013) Inflammation and liver tumorigenesis. Front Med 7:242–254

    PubMed  Google Scholar 

  17. Wang F, Meng W, Wang B, Qiao L (2014) Helicobacter pylori-induced gastric inflammation and gastric cancer. Cancer Lett 345:196–202

    CAS  PubMed  Google Scholar 

  18. Nagai H, Toyokuni S (2010) Biopersistent fiber-induced inflammation and carcinogenesis: lessons learned from asbestos toward safety of fibrous nanomaterials. Arch Biochem Biophys 502:1–7

    CAS  PubMed  Google Scholar 

  19. Hartnett L, Egan LJ (2012) Inflammation, DNA methylation and colitis-associated cancer. Carcinogenesis 33:723–731

    CAS  PubMed  Google Scholar 

  20. Nakai Y, Nonomura N (2013) Inflammation and prostate carcinogenesis. Int J Urol 20:150–160

    CAS  PubMed  Google Scholar 

  21. Borrello MG, Degl’Innocenti D, Pierotti MA (2008) Inflammation and cancer: the oncogene-driven connection. Cancer Lett 267:262–270

    CAS  PubMed  Google Scholar 

  22. West AP, Koblansky AA, Ghosh S (2006) Recognition and signaling by toll-like receptors. Annu Rev Cell Dev Biol 22:409–437

    CAS  PubMed  Google Scholar 

  23. Mantovani A, Cassatella MA, Costantini C, Jaillon S (2011) Neutrophils in the activation and regulation of innate and adaptive immunity. Nat Rev Immunol 11:519–531

    CAS  PubMed  Google Scholar 

  24. Wu Y, Antony S, Meitzler JL, Doroshow JH (2014) Molecular mechanisms underlying chronic inflammation-associated cancers. Cancer Lett 345:164–173

    CAS  PubMed  Google Scholar 

  25. Moretta A, Marcenaro E, Sivori S, Della Chiesa M, Vitale M, Moretta L (2005) Early liaisons between cells of the innate immune system in inflamed peripheral tissues. Trends Immunol 26:668–675

    CAS  PubMed  Google Scholar 

  26. Steinman RM (2012) Decisions about dendritic cells: past, present, and future. Annu Rev Immunol 30:1–22

    CAS  PubMed  Google Scholar 

  27. Fan Y, Mao R, Yang J (2013) NF-κB and STAT3 signaling pathways collaboratively link inflammation to cancer. Protein Cell 4:176–185

    CAS  PubMed  Google Scholar 

  28. Porta C, Larghi P, Rimoldi M, Totaro MG, Allavena P, Mantovani A, Sica A (2009) Cellular and molecular pathways linking inflammation and cancer. Immunobiology 214:761–777

    CAS  PubMed  Google Scholar 

  29. Coussens LM, Werb Z (2002) Inflammation and cancer. Nature 420:860–867

    CAS  PubMed Central  PubMed  Google Scholar 

  30. Martinez FO, Sica A, Mantovani A, Locati M (2008) Macrophage activation and polarization. Front Biosci 13:453–461

    CAS  PubMed  Google Scholar 

  31. Whiteside TL (2014) Regulatory T cell subsets in human cancer: are they regulating for or against tumor progression? Cancer Immunol Immunother 63:67–72

    CAS  PubMed  Google Scholar 

  32. Ostrand-Rosenberg S, Sinha P (2009) Myeloid-derived suppressor cells: linking inflammation and cancer. J Immunol 182:4499–4506

    CAS  PubMed Central  PubMed  Google Scholar 

  33. Loeb LA, Loeb KR, Anderson JP (2003) Multiple mutations and cancer. Proc Natl Acad Sci U S A 100:776–781

    CAS  PubMed Central  PubMed  Google Scholar 

  34. McLean MH, Murray GI, Stewart KN et al (2011) The inflammatory microenvironment in colorectal neoplasia. PLoS One 6:e15366

    CAS  PubMed Central  PubMed  Google Scholar 

  35. Wiseman H, Halliwell B (1996) Damage to DNA by reactive oxygen and nitrogen species: role in inflammatory disease and progression to cancer. Biochem J 313(Pt 1):17–29

    CAS  PubMed Central  PubMed  Google Scholar 

  36. Kidane D, Chae WJ, Czochor J, Eckert KA, Glazer PM, Bothwell ALM, Sweasy JB (2014) Interplay between DNA repair and inflammation, and the link to cancer. Crit Rev Biochem Mol Biol 49:116–139

    CAS  PubMed  Google Scholar 

  37. Weitzman SA, Stossel TP (1981) Mutation caused by human phagocytes. Science 212:546–547

    CAS  PubMed  Google Scholar 

  38. Weitzman SA, Stossel TP (1982) Effects of oxygen radical scavengers and antioxidants on phagocyte-induced mutagenesis. J Immunol 128:2770–2772

    CAS  PubMed  Google Scholar 

  39. Fulton AM, Loveless SE, Heppner GH (1984) Mutagenic activity of tumor-associated macrophages in Salmonella typhimurium strains TA98 and TA 100. Cancer Res 44:4308–4311

    CAS  PubMed  Google Scholar 

  40. Chong YC, Heppner GH, Paul LA, Fulton AM (1989) Macrophage-mediated induction of DNA strand breaks in target tumor cells. Cancer Res 49:6652–6657

    CAS  PubMed  Google Scholar 

  41. Weitzman SA, Weitberg AB, Clark EP, Stossel TP (1985) Phagocytes as carcinogens: malignant transformation produced by human neutrophils. Science 227:1231–1233

    CAS  PubMed  Google Scholar 

  42. Cerda S, Weitzman SA (1997) Influence of oxygen radical injury on DNA methylation. Mutat Res 386:141–152

    CAS  PubMed  Google Scholar 

  43. Shimizu T, Marusawa H, Endo Y, Chiba T (2012) Inflammation-mediated genomic instability: roles of activation-induced cytidine deaminase in carcinogenesis. Cancer Sci 103:1201–1206

    CAS  PubMed  Google Scholar 

  44. Honjo T, Kinoshita K, Muramatsu M (2002) Molecular mechanism of class switch recombination: linkage with somatic hypermutation. Annu Rev Immunol 20:165–196

    CAS  PubMed  Google Scholar 

  45. Fear DJ (2013) Mechanisms regulating the targeting and activity of activation induced cytidine deaminase. Curr Opin Immunol 25:619–628

    CAS  PubMed  Google Scholar 

  46. Okazaki I, Hiai H, Kakazu N, Yamada S, Muramatsu M, Kinoshita K, Honjo T (2003) Constitutive expression of AID leads to tumorigenesis. J Exp Med 197:1173–1181

    CAS  PubMed Central  PubMed  Google Scholar 

  47. Hofseth LJ, Khan MA, Ambrose M et al (2003) The adaptive imbalance in base excision-repair enzymes generates microsatellite instability in chronic inflammation. J Clin Invest 112:1887–1894

    CAS  PubMed Central  PubMed  Google Scholar 

  48. Imai K, Yamamoto H (2008) Carcinogenesis and microsatellite instability: the interrelationship between genetics and epigenetics. Carcinogenesis 29:673–680

    CAS  PubMed  Google Scholar 

  49. Yashiro M, Hirakawa K, Boland CR (2010) Mutations in TGFbeta-RII and BAX mediate tumor progression in the later stages of colorectal cancer with microsatellite instability. BMC Cancer 10:303

    PubMed Central  PubMed  Google Scholar 

  50. Abbas T, Keaton MA, Dutta A (2013) Genomic instability in cancer. Cold Spring Harb Perspect Biol 5(3):a0129914. doi: 10.1101/cshperspect.a012914

    Google Scholar 

  51. Schetter AJ, Heegaard NHH, Harris CC (2010) Inflammation and cancer: interweaving microRNA, free radical, cytokine and p53 pathways. Carcinogenesis 31:37–49

    CAS  PubMed Central  PubMed  Google Scholar 

  52. Petrenko O, Moll UM (2005) Macrophage migration inhibitory factor MIF interferes with the Rb-E2 F pathway. Mol Cell 17:225–236

    CAS  PubMed  Google Scholar 

  53. Hira E, Ono T, Dhar DK, El-Assal ON, Hishikawa Y, Yamanoi A, Nagasue N (2005) Overexpression of macrophage migration inhibitory factor induces angiogenesis and deteriorates prognosis after radical resection for hepatocellular carcinoma. Cancer 103:588–598

    CAS  PubMed  Google Scholar 

  54. Shun C-T, Lin J-T, Huang S-P, Lin M-T, Wu M-S (2005) Expression of macrophage migration inhibitory factor is associated with enhanced angiogenesis and advanced stage in gastric carcinomas. World J Gastroenterol 11:3767–3771

    CAS  PubMed  Google Scholar 

  55. White ES, Flaherty KR, Carskadon S, Brant A, Iannettoni MD, Yee J, Orringer MB, Arenberg DA (2003) Macrophage migration inhibitory factor and CXC chemokine expression in non-small cell lung cancer: role in angiogenesis and prognosis. Clin Cancer Res 9:853–860

    CAS  PubMed  Google Scholar 

  56. Hussain SP, Amstad P, Raja K et al (2000) Increased p53 mutation load in noncancerous colon tissue from ulcerative colitis: a cancer-prone chronic inflammatory disease. Cancer Res 60:3333–3337

    CAS  PubMed  Google Scholar 

  57. Matsumoto Y, Marusawa H, Kinoshita K, Endo Y, Kou T, Morisawa T, Azuma T, Okazaki I-M, Honjo T, Chiba T (2007) Helicobacter pylori infection triggers aberrant expression of activation-induced cytidine deaminase in gastric epithelium. Nat Med 13:470–476

    CAS  PubMed  Google Scholar 

  58. Shinmura K, Igarashi H, Goto M et al (2011) Aberrant expression and mutation-inducing activity of AID in human lung cancer. Ann Surg Oncol 18:2084–2092

    PubMed  Google Scholar 

  59. Wei J, Noto J, Zaika E, Romero-Gallo J, Correa P, El-Rifai W, Peek RM, Zaika A (2012) Pathogenic bacterium Helicobacter pylori alters the expression profile of p53 protein isoforms and p53 response to cellular stresses. Proc Natl Acad Sci U S A 109:E2543–E2550

    Google Scholar 

  60. Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144:646–674

    CAS  PubMed  Google Scholar 

  61. Bindea G, Mlecnik B, Fridman W-H, Galon J (2011) The prognostic impact of anti-cancer immune response: a novel classification of cancer patients. Semin Immunopathol 33:335–340

    CAS  PubMed Central  PubMed  Google Scholar 

  62. Schreiber RD, Old LJ, Smyth MJ (2011) Cancer immunoediting: integrating immunity's roles in cancer suppression and promotion. Science 331:1565–1570

    CAS  PubMed  Google Scholar 

  63. Dunn GP, Old LJ, Schreiber RD (2004) The immunobiology of cancer immunosurveillance and immunoediting. Immunity 21:137–148

    CAS  PubMed  Google Scholar 

  64. Bui JD, Schreiber RD (2007) Cancer immunosurveillance, immunoediting and inflammation: independent or interdependent processes? Curr Opin Immunol 19:203–208

    CAS  PubMed  Google Scholar 

  65. DeNardo DG, Andreu P, Coussens LM (2010) Interactions between lymphocytes and myeloid cells regulate pro- versus anti-tumor immunity. Cancer Metastasis Rev 29:309–316

    PubMed Central  PubMed  Google Scholar 

  66. Ruffell B, DeNardo DG, Affara NI, Coussens LM (2010) Lymphocytes in cancer development: polarization towards pro-tumor immunity. Cytokine Growth Factor Rev 21:3–10

    CAS  PubMed Central  PubMed  Google Scholar 

  67. Marcus A, Gowen BG, Thompson TW, Iannello A, Ardolino M, Deng W, Wang L, Shifrin N, Raulet DH (2014) Recognition of tumors by the innate immune system and natural killer cells. Adv Immunol 122:91–128

    CAS  PubMed  Google Scholar 

  68. Coulie PG, Van den Eynde BJ, van der Bruggen P, Boon T (2014) Tumour antigens recognized by T lymphocytes: at the core of cancer immunotherapy. Nat Rev Cancer 14:135–146

    CAS  PubMed  Google Scholar 

  69. Waldhauer I, Steinle A (2008) NK cells and cancer immunosurveillance. Oncogene 27:5932–5943

    CAS  PubMed  Google Scholar 

  70. Long EO, Kim HS, Liu D, Peterson ME, Rajagopalan S (2013) Controlling natural killer cell responses: integration of signals for activation and inhibition. Annu Rev Immunol 31:227–258

    CAS  PubMed  Google Scholar 

  71. Sancar A, Lindsey-Boltz LA, Unsal-Kaçmaz K, Linn S (2004) Molecular mechanisms of mammalian DNA repair and the DNA damage checkpoints. Annu Rev Biochem 73:39–85

    CAS  PubMed  Google Scholar 

  72. Cerboni C, Fionda C, Soriani A, Zingoni A, Doria M, Cippitelli M, Santoni A (2014) The DNA Damage Response: A Common Pathway in the Regulation of NKG2D and DNAM-1 Ligand Expression in Normal, Infected, and Cancer Cells. Front Immunol 4:508

    PubMed Central  PubMed  Google Scholar 

  73. Gasser S, Orsulic S, Brown EJ, Raulet DH (2005) The DNA damage pathway regulates innate immune system ligands of the NKG2D receptor. Nature 436:1186–1190

    CAS  PubMed Central  PubMed  Google Scholar 

  74. Mincheva-Nilsson L, Baranov V (2014) Cancer exosomes and NKG2D receptor-ligand interactions: Impairing NKG2D-mediated cytotoxicity and anti-tumour immune surveillance. Semin Cancer Biol. doi: 10.1016/j.semcancer.2014.02.010

    Google Scholar 

  75. Suzuki T, Terao S, Acharya B, Naoe M, Yamamoto S, Okamura H, Gotoh A (2010) The antitumour effect of {gamma}{delta} T-cells is enhanced by valproic acid-induced up-regulation of NKG2D ligands. Anticancer Res 30:4509–4513

    CAS  PubMed  Google Scholar 

  76. Nanbakhsh A, Pochon C, Mallavialle A, Amsellem S, Bourhis JH, Chouaib S (2014) c-Myc regulates expression of NKG2D ligands ULBP1/2/3 in AML and modulates their susceptibility to NK-mediated lysis. Blood 123:3585–3595

    CAS  PubMed Central  PubMed  Google Scholar 

  77. Smyth MJ, Swann J, Cretney E, Zerafa N, Yokoyama WM, Hayakawa Y (2005) NKG2D function protects the host from tumor initiation. J Exp Med 202:583–588

    CAS  PubMed Central  PubMed  Google Scholar 

  78. Iguchi-Manaka A, Kai H, Yamashita Y, Shibata K, Tahara-Hanaoka S, Honda S, Yasui T, Kikutani H, Shibuya K, Shibuya A (2008) Accelerated tumor growth in mice deficient in DNAM-1 receptor. J Exp Med 205:2959–2964

    CAS  PubMed Central  PubMed  Google Scholar 

  79. Guerra N, Tan YX, Joncker NT et al (2008) NKG2D-deficient mice are defective in tumor surveillance in models of spontaneous malignancy. Immunity 28:571–580

    CAS  PubMed Central  PubMed  Google Scholar 

  80. Iannello A, Raulet DH (2014) Immunosurveillance of senescent cancer cells by natural killer cells. Oncoimmunology 3:e27616

    PubMed Central  PubMed  Google Scholar 

  81. Blum JS, Wearsch PA, Cresswell P (2013) Pathways of antigen processing. Annu Rev Immunol 31:443–473

    CAS  PubMed Central  PubMed  Google Scholar 

  82. Smith-Garvin JE, Koretzky GA, Jordan MS (2009) T cell activation. Annu Rev Immunol 27:591–619

    CAS  PubMed Central  PubMed  Google Scholar 

  83. Guermonprez P, Valladeau J, Zitvogel L, Théry C, Amigorena S (2002) Antigen presentation and T cell stimulation by dendritic cells. Annu Rev Immunol 20:621–667

    CAS  PubMed  Google Scholar 

  84. Garbe Y, Maletzki C, Linnebacher M (2011) An MSI tumor specific frameshift mutation in a coding microsatellite of MSH3 encodes for HLA-A0201-restricted CD8 + cytotoxic T cell epitopes. PLoS One 6:e26517

    CAS  PubMed Central  PubMed  Google Scholar 

  85. Maletzki C, Schmidt F, Dirks WG, Schmitt M, Linnebacher M (2013) Frameshift-derived neoantigens constitute immunotherapeutic targets for patients with microsatellite-instable haematological malignancies: frameshift peptides for treating MSI + blood cancers. Eur J Cancer 49:2587–2595

    CAS  PubMed  Google Scholar 

  86. Ishikawa T, Fujita T, Suzuki Y, Okabe S, Yuasa Y, Iwai T, Kawakami Y (2003) Tumor-specific immunological recognition of frameshift-mutated peptides in colon cancer with microsatellite instability. Cancer Res 63:5564–5572

    CAS  PubMed  Google Scholar 

  87. Saeterdal I, Bjørheim J, Lislerud K et al (2001) Frameshift-mutation-derived peptides as tumor-specific antigens in inherited and spontaneous colorectal cancer. Proc Natl Acad Sci U S A 98:13255–13260

    CAS  PubMed Central  PubMed  Google Scholar 

  88. Buckowitz A, Knaebel H-P, Benner A, Bläker H, Gebert J, Kienle P, von Knebel Doeberitz M, Kloor M (2005) Microsatellite instability in colorectal cancer is associated with local lymphocyte infiltration and low frequency of distant metastases. Br J Cancer 92:1746–1753

    CAS  PubMed Central  PubMed  Google Scholar 

  89. Nakata B, Wang YQ, Yashiro M, Nishioka N, Tanaka H, Ohira M, Ishikawa T, Nishino H, Hirakawa K (2002) Prognostic value of microsatellite instability in resectable pancreatic cancer. Clin Cancer Res 8:2536–2540

    CAS  PubMed  Google Scholar 

  90. Lü B-J, Lai M, Cheng L, Xu J-Y, Huang Q (2004) Gastric medullary carcinoma, a distinct entity associated with microsatellite instability-H, prominent intraepithelial lymphocytes and improved prognosis. Histopathology 45:485–492

    PubMed  Google Scholar 

  91. Dolcetti R, Viel A, Doglioni C, Russo A, Guidoboni M, Capozzi E, Vecchiato N, Macrì E, Fornasarig M, Boiocchi M (1999) High prevalence of activated intraepithelial cytotoxic T lymphocytes and increased neoplastic cell apoptosis in colorectal carcinomas with microsatellite instability. Am J Pathol 154:1805–1813

    CAS  PubMed Central  PubMed  Google Scholar 

  92. Guidoboni M, Gafà R, Viel A et al (2001) Microsatellite instability and high content of activated cytotoxic lymphocytes identify colon cancer patients with a favorable prognosis. Am J Pathol 159:297–304

    CAS  PubMed Central  PubMed  Google Scholar 

  93. Bauer K, Nelius N, Reuschenbach M et al (2013) T cell responses against microsatellite instability-induced frameshift peptides and influence of regulatory T cells in colorectal cancer. Cancer Immunol Immunother 62:27–37

    CAS  PubMed  Google Scholar 

  94. O’Sullivan T, Saddawi-Konefka R, Vermi W et al (2012) Cancer immunoediting by the innate immune system in the absence of adaptive immunity. J Exp Med 209:1869–1882

    PubMed Central  PubMed  Google Scholar 

  95. Koebel CM, Vermi W, Swann JB, Zerafa N, Rodig SJ, Old LJ, Smyth MJ, Schreiber RD (2007) Adaptive immunity maintains occult cancer in an equilibrium state. Nature 450:903–907

    CAS  PubMed  Google Scholar 

  96. Matsushita H, Vesely MD, Koboldt DC et al (2012) Cancer exome analysis reveals a T-cell-dependent mechanism of cancer immunoediting. Nature 482:400–404

    CAS  PubMed  Google Scholar 

  97. Chang C-C, Ferrone S (2007) Immune selective pressure and HLA class I antigen defects in malignant lesions. Cancer Immunol Immunother 56:227–236

    CAS  PubMed  Google Scholar 

  98. Chretien A-S, Le Roy A, Vey N, Prebet T, Blaise D, Fauriat C, Olive D (2014) Cancer-Induced Alterations of NK-Mediated Target Recognition: Current and Investigational Pharmacological Strategies Aiming at Restoring NK-Mediated Anti-Tumor Activity. Front Immunol 5:122

    PubMed Central  PubMed  Google Scholar 

  99. Gajewski TF (2007) Failure at the effector phase: immune barriers at the level of the melanoma tumor microenvironment. Clin Cancer Res 13:5256–5261

    CAS  PubMed  Google Scholar 

  100. Seliger B (2005) Strategies of tumor immune evasion. BioDrugs 19:347–354

    CAS  PubMed  Google Scholar 

  101. Ferlito A, Elsheikh MN, Manni JJ, Rinaldo A (2007) Paraneoplastic syndromes in patients with primary head and neck cancer. Eur Arch Otorhinolaryngol 264:211–222

    PubMed  Google Scholar 

  102. Kanaji N, Watanabe N, Kita N, Bandoh S, Tadokoro A, Ishii T, Dobashi H, Matsunaga T (2014) Paraneoplastic syndromes associated with lung cancer. World J Clin Oncol 5:197–223

    PubMed Central  PubMed  Google Scholar 

  103. Karlsson M, Lindberg K, Karlén P, Ost A, Thörn M, Winqvist O, Eberhardson M (2010) Evidence for immunosurveillance in intestinal premalignant lesions. Scand J Immunol 71:362–368

    CAS  PubMed  Google Scholar 

  104. Kiran RP, Ali UA, Nisar PJ et al (2014) Risk and location of cancer in patients with preoperative colitis-associated dysplasia undergoing proctocolectomy. Ann Surg 259:302–309

    PubMed  Google Scholar 

  105. Zisman TL, Bronner MP, Rulyak S et al (2012) Prospective study of the progression of low-grade dysplasia in ulcerative colitis using current cancer surveillance guidelines. Inflamm Bowel Dis 18:2240–2246

    PubMed Central  PubMed  Google Scholar 

  106. Schwitalle Y, Kloor M, Eiermann S, Linnebacher M, Kienle P, Knaebel HP, Tariverdian M, Benner A, von Knebel Doeberitz M (2008) Immune response against frameshift-induced neopeptides in HNPCC patients and healthy HNPCC mutation carriers. Gastroenterology 134:988–997

    CAS  PubMed  Google Scholar 

  107. Zitvogel L, Galluzzi L, Smyth MJ, Kroemer G (2013) Mechanism of action of conventional and targeted anticancer therapies: reinstating immunosurveillance. Immunity 39:74–88

    CAS  PubMed  Google Scholar 

  108. Topalian SL, Weiner GJ, Pardoll DM (2011) Cancer immunotherapy comes of age. J Clin Oncol 29:4828–4836

    CAS  PubMed Central  PubMed  Google Scholar 

  109. Garrido F, Ruiz-Cabello F (1991) MHC expression on human tumors–its relevance for local tumor growth and metastasis. Semin Cancer Biol 2:3–10

    CAS  PubMed  Google Scholar 

  110. Bernal M, Ruiz-Cabello F, Concha A, Paschen A, Garrido F (2012) Implication of the β2-microglobulin gene in the generation of tumor escape phenotypes. Cancer Immunol Immunother 61:1359–1371

    PubMed  Google Scholar 

  111. Kloor M, Michel S, Buckowitz B et al (2007) Beta2-microglobulin mutations in microsatellite unstable colorectal tumors. Int J Cancer 121:454–458

    CAS  PubMed  Google Scholar 

  112. Tikidzhieva A, Benner A, Michel S, Formentini A, Link K-H, Dippold W, von Knebel Doeberitz M, Kornmann M, Kloor M (2012) Microsatellite instability and Beta2-Microglobulin mutations as prognostic markers in colon cancer: results of the FOGT-4 trial. Br J Cancer 106:1239–1245

    CAS  PubMed Central  PubMed  Google Scholar 

  113. Purdy AK, Campbell KS (2009) Natural killer cells and cancer: regulation by the killer cell Ig-like receptors (KIR). Cancer Biol Ther 8:2211–2220

    PubMed  Google Scholar 

  114. Tu MM, Mahmoud AB, Wight A, Mottashed A, Bélanger S, Rahim MMA, Abou-Samra E, Makrigiannis AP (2014) Ly49 family receptors are required for cancer immunosurveillance mediated by natural killer cells. Cancer Res 74:3684–3694

    CAS  PubMed  Google Scholar 

  115. Placke T, Kopp H-G, Salih HR (2011) Modulation of natural killer cell anti-tumor reactivity by platelets. J Innate Immun 3:374–382

    CAS  PubMed  Google Scholar 

  116. Palumbo JS, Barney KA, Blevins EA et al (2008) Factor XIII transglutaminase supports hematogenous tumor cell metastasis through a mechanism dependent on natural killer cell function. J Thromb Haemost 6:812–819

    CAS  PubMed  Google Scholar 

  117. Placke T, Salih HR, Kopp H-G (2012) GITR ligand provided by thrombopoietic cells inhibits NK cell antitumor activity. J Immunol 189:154–160

    CAS  PubMed  Google Scholar 

  118. Giardiello FM, Hamilton SR, Krush AJ, Piantadosi S, Hylind LM, Celano P, Booker S V, Robinson CR, Offerhaus GJ (1993) Treatment of colonic and rectal adenomas with sulindac in familial adenomatous polyposis. N Engl J Med 328:1313–1316

    Google Scholar 

  119. Labayle D, Fischer D, Vielh P, Drouhin F, Pariente A, Bories C, Duhamel O, Trousset M, Attali P (1991) Sulindac causes regression of rectal polyps in familial adenomatous polyposis. Gastroenterology 101:635–639

    CAS  PubMed  Google Scholar 

  120. Phillips RKS, Wallace MH, Lynch PM et al (2002) A randomised, double blind, placebo controlled study of celecoxib, a selective cyclooxygenase 2 inhibitor, on duodenal polyposis in familial adenomatous polyposis. Gut 50:857–860

    CAS  PubMed Central  PubMed  Google Scholar 

  121. Burn J, Bishop DT, Chapman PD et al (2011) A randomized placebo-controlled prevention trial of aspirin and/or resistant starch in young people with familial adenomatous polyposis. Cancer Prev Res (Phila) 4:655–665

    CAS  Google Scholar 

  122. Quail DF, Joyce JA (2013) Microenvironmental regulation of tumor progression and metastasis. Nat Med 19:1423–1437

    CAS  PubMed Central  PubMed  Google Scholar 

  123. Reisfeld RA (2013) The tumor microenvironment: a target for combination therapy of breast cancer. Crit Rev Oncog 18:115–133

    PubMed  Google Scholar 

  124. Ataie-Kachoie P, Pourgholami MH, Morris DL (2013) Inhibition of the IL-6 signaling pathway: a strategy to combat chronic inflammatory diseases and cancer. Cytokine Growth Factor Rev 24:163–173

    CAS  PubMed  Google Scholar 

  125. Aggarwal BB, Vijayalekshmi R V, Sung B (2009) Targeting inflammatory pathways for prevention and therapy of cancer: short-term friend, long-term foe. Clin Cancer Res 15:425–430

    CAS  PubMed  Google Scholar 

  126. Pardoll DM (2012) The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer 12:252–264

    CAS  PubMed  Google Scholar 

  127. Von Knebel Doeberitz M, Kloor M (2013) Towards a vaccine to prevent cancer in Lynch syndrome patients. Fam Cancer 12:307–312

    Google Scholar 

Download references

Acknowledgements

The author is the recipient of a Canadian Cancer Society Career Development Award in Prevention.

Author information

Authors and Affiliations

  1. Department of Pediatrics, University of British Columbia, V5Z 4H4, Vancouver, BC, Canada

    Gregor Reid

Authors
  1. Gregor Reid
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Gregor Reid .

Editor information

Editors and Affiliations

  1. Child & Family Research Institute, University of British Columbia, Pediatrics, Vancouver, British Columbia, Canada

    Chris Maxwell

  2. Dept of Cellular & Physiological Sciences, University of British Columbia, Dept. of Cellular & Physiological Sciences, Vancouver, British Columbia, Canada

    Cal Roskelley

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Reid, G. (2015). Immunomodulation and Genomic Instability. In: Maxwell, C., Roskelley, C. (eds) Genomic Instability and Cancer Metastasis. Cancer Metastasis - Biology and Treatment, vol 20. Springer, Cham. https://doi.org/10.1007/978-3-319-12136-9_8

Download citation

Publish with us

Policies and ethics

Search

Navigation