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Relationship Between Th17 and Regulatory T Cells in the Tumor Environment

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Innate Immune Regulation and Cancer Immunotherapy

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Abstract

Th17 cells are thought to mediate inflammatory responses, whereas regulatory T (Treg) cells inhibit tumor immunity and reduce inflammation. Both Th17 and Treg cells infiltrate the tumor microenvironment. In this chapter, we discuss the distribution, migration, regulation, and function of Th17 cells in the tumor microenvironment, and the relationship between Th17 and Treg cells in the context of inflammation and tumorigenesis.

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References

  • Acosta-Rodriguez EV et al (2007a) Surface phenotype and antigenic specificity of human interleukin 17-producing T helper memory cells. Nat Immunol 8(6):639–646

    Article  PubMed  CAS  Google Scholar 

  • Acosta-Rodriguez EV et al (2007b) Interleukins 1beta and 6 but not transforming growth factor-beta are essential for the differentiation of interleukin 17-producing human T helper cells. Nat Immunol 8(9):942–949

    Article  PubMed  CAS  Google Scholar 

  • Aggarwal S, Gurney AL (2002) IL-17: prototype member of an emerging cytokine family. J Leukoc Biol 71(1):1–8

    PubMed  CAS  Google Scholar 

  • Allakhverdi Z et al (2006) Expression of CD103 identifies human regulatory T-cell subsets. J Allergy Clin Immunol 118(6):1342–1349

    Article  PubMed  CAS  Google Scholar 

  • Almeida JR et al (2007) Superior control of HIV-1 replication by CD8+ T cells is reflected by their avidity, polyfunctionality, and clonal turnover. J Exp Med 204(10):2473–2485

    Article  PubMed  CAS  Google Scholar 

  • Apostolou I et al (2002) Origin of regulatory T cells with known specificity for antigen. Nat Immunol 3(8):756–763

    PubMed  CAS  Google Scholar 

  • Appay V et al (2006) New generation vaccine induces effective melanoma-specific CD8+ T cells in the circulation but not in the tumor site. J Immunol 177(3):1670–1678

    PubMed  CAS  Google Scholar 

  • Atarashi K et al (2008) ATP drives lamina propria T(H)17 cell differentiation. Nature 455(7214):808–812

    Article  PubMed  CAS  Google Scholar 

  • Attig S et al (2009) Simultaneous infiltration of polyfunctional effector and suppressor T cells into renal cell carcinomas. Cancer Res 69(21):8412–8419

    Article  PubMed  CAS  Google Scholar 

  • Awasthi A et al (2007) A dominant function for interleukin 27 in generating interleukin 10-producing anti-inflammatory T cells. Nat Immunol 8(12):1380–1389

    Article  PubMed  CAS  Google Scholar 

  • Baecher-Allan C et al (2001) CD4+ CD25high regulatory cells in human peripheral blood. J Immunol 167(3):1245–1253

    PubMed  CAS  Google Scholar 

  • Barnett B et al (2005) Regulatory T cells in ovarian cancer: biology and therapeutic potential. Am J Reprod Immunol 54(6):369–377

    Article  PubMed  CAS  Google Scholar 

  • Barnett BG et al (2008) Regulatory T cells: a new frontier in cancer immunotherapy. Adv Exp Med Biol 622:255–260

    Article  PubMed  CAS  Google Scholar 

  • Becker C et al (2004) TGF-beta suppresses tumor progression in colon cancer by inhibition of IL-6 trans-signaling. Immunity 21(4):491–501

    Article  PubMed  CAS  Google Scholar 

  • Bell D et al (1999) In breast carcinoma tissue, immature dendritic cells reside within the tumor, whereas mature dendritic cells are located in peritumoral areas. J Exp Med 190(10):1417–1426

    Article  PubMed  CAS  Google Scholar 

  • Benchetrit F et al (2002) Interleukin-17 inhibits tumor cell growth by means of a T-cell-dependent mechanism. Blood 99(6):2114–2121

    Article  PubMed  CAS  Google Scholar 

  • Bensinger SJ et al (2001) Major histocompatibility complex class II-positive cortical epithelium mediates the selection of CD4(+)25(+) immunoregulatory T cells. J Exp Med 194(4):427–438

    Article  PubMed  CAS  Google Scholar 

  • Benson MJ et al (2007) All-trans retinoic acid mediates enhanced T reg cell growth, differentiation, and gut homing in the face of high levels of co-stimulation. J Exp Med 204(8):1765–1774

    Article  PubMed  CAS  Google Scholar 

  • Berendt MJ, North RJ (1980) T-cell-mediated suppression of anti-tumor immunity. An explanation for progressive growth of an immunogenic tumor. J Exp Med 151(1):69–80

    Article  PubMed  CAS  Google Scholar 

  • Bettelli E et al (2006) Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells. Nature 441(7090):235–238

    Article  PubMed  CAS  Google Scholar 

  • Boniface K et al (2009) Prostaglandin E2 regulates Th17 cell differentiation and function through cyclic AMP and EP2/EP4 receptor signaling. J Exp Med 206(3):535–548

    Article  PubMed  CAS  Google Scholar 

  • Bopp T et al (2007) Cyclic adenosine monophosphate is a key component of regulatory T cell-mediated suppression. J Exp Med 204(6):1303–1310

    Article  PubMed  CAS  Google Scholar 

  • Borsellino G et al (2007) Expression of ectonucleotidase CD39 by Foxp3+ Treg cells: hydrolysis of extracellular ATP and immune suppression. Blood 110(4):1225–1232

    Article  PubMed  CAS  Google Scholar 

  • Bursuker I, North RJ (1984) Generation and decay of the immune response to a progressive fibrosarcoma. II. Failure to demonstrate postexcision immunity after the onset of T cell-mediated suppression of immunity. J Exp Med 159(5):1312–1321

    Article  PubMed  CAS  Google Scholar 

  • Cavani A et al (2003) Human CD25+ regulatory T cells maintain immune tolerance to nickel in healthy, nonallergic individuals. J Immunol 171(11):5760–5768

    PubMed  CAS  Google Scholar 

  • Cederbom L, Hall H, Ivars F (2000) CD4+ CD25+ regulatory T cells down-regulate co-stimulatory molecules on antigen-presenting cells. Eur J Immunol 30(6):1538–1543

    Article  PubMed  CAS  Google Scholar 

  • Chen W et al (2003) Conversion of peripheral CD4+ CD25- naive T cells to CD4+ CD25+ regulatory T cells by TGF-beta induction of transcription factor Foxp3. J Exp Med 198(12):1875–1886

    Article  PubMed  CAS  Google Scholar 

  • Chen X et al (2006) Pertussis toxin as an adjuvant suppresses the number and function of CD4+ CD25+ T regulatory cells. Eur J Immunol 36(3):671–680

    Article  PubMed  CAS  Google Scholar 

  • Chizzolini C et al (2008) Prostaglandin E2 synergistically with interleukin-23 favors human Th17 expansion. Blood 112(9):3696–3703

    Article  PubMed  CAS  Google Scholar 

  • Chung Y et al (2009) Critical regulation of early Th17 cell differentiation by interleukin-1 signaling. Immunity 30(4):576–587

    Article  PubMed  CAS  Google Scholar 

  • Collins AV et al (2002) The interaction properties of costimulatory molecules revisited. Immunity 17(2):201–210

    Article  PubMed  CAS  Google Scholar 

  • Coombes JL et al (2007) A functionally specialized population of mucosal CD103+ DCs induces Foxp3+ regulatory T cells via a TGF-beta and retinoic acid-dependent mechanism. J Exp Med 204(8):1757–1764

    Article  PubMed  CAS  Google Scholar 

  • Coquet JM et al (2008) Diverse cytokine production by NKT cell subsets and identification of an IL-17-producing CD4-NK1.1- NKT cell population. Proc Natl Acad Sci USA 105(32):11287–11292

    Article  PubMed  CAS  Google Scholar 

  • Cosmi L et al (2008) Human interleukin 17-producing cells originate from a CD161+ CD4+ T cell precursor. J Exp Med 205(8):1903–1916

    Article  PubMed  CAS  Google Scholar 

  • Coussens LM, Werb Z (2002) Inflammation and cancer. Nature 420(6917):860–867

    Article  PubMed  CAS  Google Scholar 

  • Curiel TJ et al (2003) Blockade of B7-H1 improves myeloid dendritic cell-mediated antitumor immunity. Nat Med 9(5):562–567

    Article  PubMed  CAS  Google Scholar 

  • Curiel TJ et al (2004) Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nat Med 10(9):942–949

    Article  PubMed  CAS  Google Scholar 

  • Deaglio S et al (2007) Adenosine generation catalyzed by CD39 and CD73 expressed on regulatory T cells mediates immune suppression. J Exp Med 204(6):1257–1265

    Article  PubMed  CAS  Google Scholar 

  • Erdman SE et al (2003) CD4(+)CD25(+) regulatory lymphocytes require interleukin 10 to interrupt colon carcinogenesis in mice. Cancer Res 63(18):6042–6050

    PubMed  CAS  Google Scholar 

  • Erdman SE et al (2005) CD4+ CD25+ regulatory lymphocytes induce regression of intestinal tumors in ApcMin/+ mice. Cancer Res 65(10):3998–4004

    Article  PubMed  CAS  Google Scholar 

  • Fletcher JM et al (2009) CD39+ Foxp3+ regulatory T Cells suppress pathogenic Th17 cells and are impaired in multiple sclerosis. J Immunol 183(11):7602–7610

    Article  PubMed  CAS  Google Scholar 

  • Fossiez F et al (1996) T cell interleukin-17 induces stromal cells to produce proinflammatory and hematopoietic cytokines. J Exp Med 183(6):2593–2603

    Article  PubMed  CAS  Google Scholar 

  • Freeman GJ et al (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

    Article  PubMed  CAS  Google Scholar 

  • Fushimi T et al (2000) Macrophage inflammatory protein 3alpha transgene attracts dendritic cells to established murine tumors and suppresses tumor growth. J Clin Invest 105(10):1383–1393

    Article  PubMed  CAS  Google Scholar 

  • Gondek DC et al (2005) Cutting edge: contact-mediated suppression by CD4+ CD25+ regulatory cells involves a granzyme B-dependent, perforin-independent mechanism. J Immunol 174(4):1783–1786

    PubMed  CAS  Google Scholar 

  • Gounaris E et al (2009) T-regulatory cells shift from a protective anti-inflammatory to a cancer-promoting proinflammatory phenotype in polyposis. Cancer Res 69(13):5490–5497

    Article  PubMed  CAS  Google Scholar 

  • Greenhough A et al (2009) The COX-2/PGE2 pathway: key roles in the hallmarks of cancer and adaptation to the tumour microenvironment. Carcinogenesis 30(3):377–386

    Article  PubMed  CAS  Google Scholar 

  • Grohmann U et al (2002) CTLA-4-Ig regulates tryptophan catabolism in vivo. Nat Immunol 3(11):1097–1101

    Article  PubMed  CAS  Google Scholar 

  • Gu Y et al (2008) Interleukin 10 suppresses Th17 cytokines secreted by macrophages and T cells. Eur J Immunol 38(7):1807–1813

    Article  PubMed  CAS  Google Scholar 

  • Hirahara N et al (2001) Inoculation of human interleukin-17 gene-transfected Meth-A fibrosarcoma cells induces T cell-dependent tumor-specific immunity in mice. Oncology 61(1):79–89

    Article  PubMed  CAS  Google Scholar 

  • Hoffmann P et al (2004) Large-scale in vitro expansion of polyclonal human CD4(+)CD25high regulatory T cells. Blood 104(3):895–903

    Article  PubMed  CAS  Google Scholar 

  • Honorati MC et al (2006) Interleukin-17, a regulator of angiogenic factor release by synovial fibroblasts. Osteoarthr Cartil 14(4):345–352

    Article  PubMed  CAS  Google Scholar 

  • Horlock C et al (2009) The effects of trastuzumab on the CD4+ CD25+ FoxP3+ and CD4+ IL17A+ T-cell axis in patients with breast cancer. Br J Cancer 100(7):1061–1067

    Article  PubMed  CAS  Google Scholar 

  • Huehn J, Polansky JK, Hamann A (2009) Epigenetic control of FOXP3 expression: the key to a stable regulatory T-cell lineage? Nat Rev Immunol 9(2):83–89

    Article  PubMed  CAS  Google Scholar 

  • Hultkrantz S, Ostman S, Telemo E (2005) Induction of antigen-specific regulatory T cells in the liver-draining celiac lymph node following oral antigen administration. Immunology 116(3):362–372

    Article  PubMed  CAS  Google Scholar 

  • Huppert J et al (2010) Cellular mechanisms of IL-17-induced blood-brain barrier disruption. FASEB J 24(4):1023–1034

    Article  PubMed  CAS  Google Scholar 

  • Iellem A et al (2001) Unique chemotactic response profile and specific expression of chemokine receptors CCR4 and CCR8 by CD4(+)CD25(+) regulatory T cells. J Exp Med 194(6):847–853

    Article  PubMed  CAS  Google Scholar 

  • Iellem A, Colantonio L, D’Ambrosio D (2003) Skin-versus gut-skewed homing receptor expression and intrinsic CCR4 expression on human peripheral blood CD4+ CD25+ suppressor T cells. Eur J Immunol 33(6):1488–1496

    Article  PubMed  CAS  Google Scholar 

  • Inozume T et al (2009) IL-17 secreted by tumor reactive T cells induces IL-8 release by human renal cancer cells. J Immunother 32(2):109–117

    Article  PubMed  CAS  Google Scholar 

  • Ishibashi Y et al (2006) Expression of Foxp3 in non-small cell lung cancer patients is significantly higher in tumor tissues than in normal tissues, especially in tumors smaller than 30 mm. Oncol Rep 15(5):1315–1319

    PubMed  CAS  Google Scholar 

  • Ivanov II et al (2006) The orphan nuclear receptor RORgammat directs the differentiation program of proinflammatory IL-17+ T helper cells. Cell 126(6):1121–1133

    Article  PubMed  CAS  Google Scholar 

  • Jeron A et al (2009) Frequency and gene expression profile of regulatory T cells in renal cell carcinoma. Tumour Biol 30(3):160–170

    Article  PubMed  CAS  Google Scholar 

  • Kang SG et al (2007) Vitamin A metabolites induce gut-homing FoxP3+ regulatory T cells. J Immunol 179(6):3724–3733

    PubMed  CAS  Google Scholar 

  • Kehlen A et al (1999) Interleukin-17 stimulates the expression of IkappaB alpha mRNA and the secretion of IL-6 and IL-8 in glioblastoma cell lines. J Neuroimmunol 101(1):1–6

    Article  PubMed  CAS  Google Scholar 

  • Khader SA et al (2005) IL-23 compensates for the absence of IL-12p70 and is essential for the IL-17 response during tuberculosis but is dispensable for protection and antigen-specific IFN-gamma responses if IL-12p70 is available. J Immunol 175(2):788–795

    PubMed  CAS  Google Scholar 

  • Kimura A, Naka T, Kishimoto T (2007) IL-6-dependent and -independent pathways in the development of interleukin 17-producing T helper cells. Proc Natl Acad Sci USA 104(29):12099–12104

    Article  PubMed  CAS  Google Scholar 

  • Kirkham BW et al (2006) Synovial membrane cytokine expression is predictive of joint damage progression in rheumatoid arthritis: a two-year prospective study (the DAMAGE study cohort). Arthritis Rheum 54(4):1122–1131

    Article  PubMed  CAS  Google Scholar 

  • Kleeff J et al (1999) Detection and localization of Mip-3alpha/LARC/Exodus, a macrophage proinflammatory chemokine, and its CCR6 receptor in human pancreatic cancer. Int J Cancer 81(4):650–657

    Article  PubMed  CAS  Google Scholar 

  • Kolls JK, Linden A (2004) Interleukin-17 family members and inflammation. Immunity 21(4):467–476

    Article  PubMed  CAS  Google Scholar 

  • Korn T et al (2007) IL-21 initiates an alternative pathway to induce proinflammatory T(H)17 cells. Nature 448(7152):484–487

    Article  PubMed  CAS  Google Scholar 

  • Kottke T et al (2007) Induction of hsp70-mediated Th17 autoimmunity can be exploited as immunotherapy for metastatic prostate cancer. Cancer Res 67(24):11970–11979

    Article  PubMed  CAS  Google Scholar 

  • Koyama K et al (2008) Reciprocal CD4+ T-cell balance of effector CD62Llow CD4+ and CD62LhighCD25+ CD4+ regulatory T cells in small cell lung cancer reflects disease stage. Clin Cancer Res 14(21):6770–6779

    Article  PubMed  CAS  Google Scholar 

  • Kryczek I et al (2006a) Cutting edge: induction of B7-H4 on APCs through IL-10: novel suppressive mode for regulatory T cells. J Immunol 177(1):40–44

    PubMed  CAS  Google Scholar 

  • Kryczek I et al (2006b) B7-H4 expression identifies a novel suppressive macrophage population in human ovarian carcinoma. J Exp Med 203(4):871–881

    Article  PubMed  CAS  Google Scholar 

  • Kryczek I et al (2007a) Cutting edge: Th17 and regulatory T cell dynamics and the regulation by IL-2 in the tumor microenvironment. J Immunol 178(11):6730–6733

    PubMed  CAS  Google Scholar 

  • Kryczek I et al (2007b) Cutting edge: opposite effects of IL-1 and IL-2 on the regulation of IL-17+ T cell pool IL-1 subverts IL-2-mediated suppression. J Immunol 179(3):1423–1426

    PubMed  CAS  Google Scholar 

  • Kryczek I et al (2007c) Relationship between B7-H4, regulatory T cells, and patient outcome in human ovarian carcinoma. Cancer Res 67(18):8900–8905

    Article  PubMed  CAS  Google Scholar 

  • Kryczek I et al (2008a) Induction of IL-17+ T cell trafficking and development by IFN-gamma: mechanism and pathological relevance in psoriasis. J Immunol 181(7):4733–4741

    PubMed  CAS  Google Scholar 

  • Kryczek I et al (2008b) Cutting edge: IFN-gamma enables APC to promote memory Th17 and abate Th1 cell development. J Immunol 181(9):5842–5846

    PubMed  CAS  Google Scholar 

  • Kryczek I et al (2009a) Phenotype, distribution, generation, and functional and clinical relevance of Th17 cells in the human tumor environments. Blood 114(6):1141–1149

    Article  PubMed  CAS  Google Scholar 

  • Kryczek I et al (2009b) Endogenous IL-17 contributes to reduced tumor growth and metastasis. Blood 114(2):357–359

    Article  PubMed  CAS  Google Scholar 

  • Kryczek I et al (2009c) FOXP3 defines regulatory T cells in human tumor and autoimmune disease. Cancer Res 69(9):3995–4000

    Article  PubMed  CAS  Google Scholar 

  • Kuang DM et al (2010) Activated monocytes in peritumoral stroma of hepatocellular carcinoma promote expansion of memory T helper 17 cells. Hepatology 51(1):154–164

    Article  PubMed  CAS  Google Scholar 

  • Kundu JK, Surh YJ (2008) Inflammation: gearing the journey to cancer. Mutat Res 659(1–2):15–30

    PubMed  CAS  Google Scholar 

  • Langowski JL et al (2006) IL-23 promotes tumour incidence and growth. Nature 442(7101):461–465

    Article  PubMed  CAS  Google Scholar 

  • Lau KM et al (2007) Increase in circulating Foxp3+ CD4+ CD25(high) regulatory T cells in nasopharyngeal carcinoma patients. Br J Cancer 96(4):617–622

    Article  PubMed  CAS  Google Scholar 

  • Laurence A et al (2007) Interleukin-2 signaling via STAT5 constrains T helper 17 cell generation. Immunity 26(3):371–381

    Article  PubMed  CAS  Google Scholar 

  • Lin WW, Karin M (2007) A cytokine-mediated link between innate immunity, inflammation, and cancer. J Clin Invest 117(5):1175–1183

    Article  PubMed  CAS  Google Scholar 

  • Liu XK, Clements JL, Gaffen SL (2005) Signaling through the murine T cell receptor induces IL-17 production in the absence of costimulation, IL-23 or dendritic cells. Mol Cells 20(3):339–347

    PubMed  CAS  Google Scholar 

  • Liyanage UK et al (2002) Prevalence of regulatory T cells is increased in peripheral blood and tumor microenvironment of patients with pancreas or breast adenocarcinoma. J Immunol 169(5):2756–2761

    PubMed  CAS  Google Scholar 

  • Makita S et al (2004) CD4+ CD25bright T cells in human intestinal lamina propria as regulatory cells. J Immunol 173(5):3119–3130

    PubMed  CAS  Google Scholar 

  • Maloy KJ et al (2003) CD4+ CD25+ T(R) cells suppress innate immune pathology through cytokine-dependent mechanisms. J Exp Med 197(1):111–119

    Article  PubMed  CAS  Google Scholar 

  • Manel N, Unutmaz D, Littman DR (2008) The differentiation of human T(H)-17 cells requires transforming growth factor-beta and induction of the nuclear receptor RORgammat. Nat Immunol 9(6):641–649

    Article  PubMed  CAS  Google Scholar 

  • Mangan PR et al (2006) Transforming growth factor-beta induces development of the T(H)17 lineage. Nature 441(7090):231–234

    Article  PubMed  CAS  Google Scholar 

  • Mantovani A et al (2008) Cancer-related inflammation. Nature 454(7203):436–444

    Article  PubMed  CAS  Google Scholar 

  • Martin-Orozco N et al (2009) T helper 17 cells promote cytotoxic T cell activation in tumor immunity. Immunity 31(5):787–798

    Article  PubMed  CAS  Google Scholar 

  • Meloni F et al (2006) Foxp3 expressing CD4+ CD25+ and CD8+ CD28- T regulatory cells in the peripheral blood of patients with lung cancer and pleural mesothelioma. Hum Immunol 67(1–2):1–12

    Article  PubMed  CAS  Google Scholar 

  • Michel ML et al (2007) Identification of an IL-17-producing NK1.1(neg) iNKT cell population involved in airway neutrophilia. J Exp Med 204(5):995–1001

    Article  PubMed  CAS  Google Scholar 

  • Misra N et al (2004) Cutting edge: human CD4+ CD25+ T cells restrain the maturation and antigen-presenting function of dendritic cells. J Immunol 172(8):4676–4680

    PubMed  CAS  Google Scholar 

  • Miyahara Y et al (2008) Generation and regulation of human CD4+ IL-17-producing T cells in ovarian cancer. Proc Natl Acad Sci USA 105(40):15505–15510

    Article  PubMed  CAS  Google Scholar 

  • Montufar-Solis D et al (2008) Massive but selective cytokine dysregulation in the colon of IL-10−/− mice revealed by multiplex analysis. Int Immunol 20(1):141–154

    Article  PubMed  CAS  Google Scholar 

  • Mucida D et al (2007) Reciprocal TH17 and regulatory T cell differentiation mediated by retinoic acid. Science 317(5835):256–260

    Article  PubMed  CAS  Google Scholar 

  • Muranski P et al (2008) Tumor-specific Th17-polarized cells eradicate large established melanoma. Blood 112(2):362–373

    Article  PubMed  CAS  Google Scholar 

  • Muraoka RS et al (2002) Blockade of TGF-beta inhibits mammary tumor cell viability, migration, and metastases. J Clin Invest 109(12):1551–1559

    PubMed  CAS  Google Scholar 

  • Nakamura K, Kitani A, Strober W (2001) Cell contact-dependent immunosuppression by CD4(+)CD25(+) regulatory T cells is mediated by cell surface-bound transforming growth factor beta. J Exp Med 194(5):629–644

    Article  PubMed  CAS  Google Scholar 

  • North RJ, Bursuker I (1984) Generation and decay of the immune response to a progressive fibrosarcoma. I. Ly-1+ 2- suppressor T cells down-regulate the generation of Ly-1-2+ effector T cells. J Exp Med 159(5):1295–1311

    Article  PubMed  CAS  Google Scholar 

  • Numasaki M et al (2003) Interleukin-17 promotes angiogenesis and tumor growth. Blood 101(7):2620–2627

    Article  PubMed  CAS  Google Scholar 

  • Numasaki M, Lotze MT, Sasaki H (2004) Interleukin-17 augments tumor necrosis factor-alpha-induced elaboration of proangiogenic factors from fibroblasts. Immunol Lett 93(1):39–43

    Article  PubMed  CAS  Google Scholar 

  • Numasaki M et al (2005) IL-17 enhances the net angiogenic activity and in vivo growth of human non-small cell lung cancer in SCID mice through promoting CXCR-2-dependent angiogenesis. J Immunol 175(9):6177–6189

    PubMed  CAS  Google Scholar 

  • Nurieva R et al (2007) Essential autocrine regulation by IL-21 in the generation of inflammatory T cells. Nature 448(7152):480–483

    Article  PubMed  CAS  Google Scholar 

  • Oehler-Janne C et al (2008) HIV-specific differences in outcome of squamous cell carcinoma of the anal canal: a multicentric cohort study of HIV-positive patients receiving highly active antiretroviral therapy. J Clin Oncol 26(15):2550–2557

    Article  PubMed  Google Scholar 

  • Onizuka S et al (1999) Tumor rejection by in vivo administration of anti-CD25 (interleukin-2 receptor alpha) monoclonal antibody. Cancer Res 59(13):3128–3133

    PubMed  CAS  Google Scholar 

  • Ormandy LA et al (2005) Increased populations of regulatory T cells in peripheral blood of patients with hepatocellular carcinoma. Cancer Res 65(6):2457–2464

    Article  PubMed  CAS  Google Scholar 

  • Park H et al (2005) A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17. Nat Immunol 6(11):1133–1141

    Article  PubMed  CAS  Google Scholar 

  • Pasare C, Medzhitov R (2003) Toll pathway-dependent blockade of CD4+ CD25+ T cell-mediated suppression by dendritic cells. Science 299(5609):1033–1036

    Article  PubMed  CAS  Google Scholar 

  • Pellegrini M et al (2009) Adjuvant IL-7 antagonizes multiple cellular and molecular inhibitory networks to enhance immunotherapies. Nat Med 15(5):528–536

    Article  PubMed  CAS  Google Scholar 

  • Piccirillo CA et al (2002) CD4(+)CD25(+) regulatory T cells can mediate suppressor function in the absence of transforming growth factor beta1 production and responsiveness. J Exp Med 196(2):237–246

    Article  PubMed  CAS  Google Scholar 

  • Precopio ML et al (2007) Immunization with vaccinia virus induces polyfunctional and phenotypically distinctive CD8(+) T cell responses. J Exp Med 204(6):1405–1416

    Article  PubMed  CAS  Google Scholar 

  • Roark CL et al (2007) Exacerbation of collagen-induced arthritis by oligoclonal, IL-17-producing gamma delta T cells. J Immunol 179(8):5576–5583

    PubMed  CAS  Google Scholar 

  • Romani L et al (2008) Defective tryptophan catabolism underlies inflammation in mouse chronic granulomatous disease. Nature 451(7175):211–215

    Article  PubMed  CAS  Google Scholar 

  • Sakaguchi S (2001) Policing the regulators. Nat Immunol 2(4):283–284

    Article  PubMed  CAS  Google Scholar 

  • Sakaguchi S (2005) Naturally arising Foxp3-expressing CD25+ CD4+ regulatory T cells in immunological tolerance to self and non-self. Nat Immunol 6(4):345–352

    Article  PubMed  CAS  Google Scholar 

  • Sasada T et al (2003) CD4+ CD25+ regulatory T cells in patients with gastrointestinal malignancies: possible involvement of regulatory T cells in disease progression. Cancer 98(5):1089–1099

    Article  PubMed  Google Scholar 

  • Sato E et al (2005) Intraepithelial CD8+ tumor-infiltrating lymphocytes and a high CD8+/regulatory T cell ratio are associated with favorable prognosis in ovarian cancer. Proc Natl Acad Sci USA 102(51):18538–18543

    Article  PubMed  CAS  Google Scholar 

  • Schnurr M et al (2005a) Extracellular nucleotide signaling by P2 receptors inhibits IL-12 and enhances IL-23 expression in human dendritic cells: a novel role for the cAMP pathway. Blood 105(4):1582–1589

    Article  PubMed  CAS  Google Scholar 

  • Schnurr M et al (2005b) Tumor antigen processing and presentation depend critically on dendritic cell type and the mode of antigen delivery. Blood 105(6):2465–2472

    Article  PubMed  CAS  Google Scholar 

  • Sfanos KS et al (2008) Phenotypic analysis of prostate-infiltrating lymphocytes reveals TH17 and Treg skewing. Clin Cancer Res 14(11):3254–3261

    Article  PubMed  CAS  Google Scholar 

  • Sharma MD et al (2009) Indoleamine 2,3-dioxygenase controls conversion of Foxp3+ Tregs to TH17-like cells in tumor-draining lymph nodes. Blood 113(24):6102–6111

    Article  PubMed  CAS  Google Scholar 

  • Siddiqui SA et al (2007) Tumor-infiltrating Foxp3-CD4+ CD25+ T cells predict poor survival in renal cell carcinoma. Clin Cancer Res 13(7):2075–2081

    Article  PubMed  CAS  Google Scholar 

  • Sitohy B et al (2008) Basal lymphoid aggregates in ulcerative colitis colon: a site for regulatory T cell action. Clin Exp Immunol 151(2):326–333

    Article  PubMed  CAS  Google Scholar 

  • Stark MA et al (2005) Phagocytosis of apoptotic neutrophils regulates granulopoiesis via IL-23 and IL-17. Immunity 22(3):285–294

    Article  PubMed  CAS  Google Scholar 

  • Stassen M et al (2004) Human CD25+ regulatory T cells: two subsets defined by the integrins alpha 4 beta 7 or alpha 4 beta 1 confer distinct suppressive properties upon CD4+ T helper cells. Eur J Immunol 34(5):1303–1311

    Article  PubMed  CAS  Google Scholar 

  • Stumhofer JS et al (2007) Interleukins 27 and 6 induce STAT3-mediated T cell production of interleukin 10. Nat Immunol 8(12):1363–1371

    Article  PubMed  CAS  Google Scholar 

  • Sun CM et al (2007) Small intestine lamina propria dendritic cells promote de novo generation of Foxp3 T reg cells via retinoic acid. J Exp Med 204(8):1775–1785

    Article  PubMed  CAS  Google Scholar 

  • Taams LS et al (2005) Modulation of monocyte/macrophage function by human CD4+ CD25+ regulatory T cells. Hum Immunol 66(3):222–230

    Article  PubMed  CAS  Google Scholar 

  • Takahashi H et al (2005) Interleukin-17 enhances bFGF-, HGF- and VEGF-induced growth of vascular endothelial cells. Immunol Lett 98(2):189–193

    Article  PubMed  CAS  Google Scholar 

  • Takatori H et al (2009) Lymphoid tissue inducer-like cells are an innate source of IL-17 and IL-22. J Exp Med 206(1):35–41

    Article  PubMed  CAS  Google Scholar 

  • Tartour E et al (1999) Interleukin 17, a T-cell-derived cytokine, promotes tumorigenicity of human cervical tumors in nude mice. Cancer Res 59(15):3698–3704

    PubMed  CAS  Google Scholar 

  • Teicher BA (2007) Transforming growth factor-beta and the immune response to malignant disease. Clin Cancer Res 13(21):6247–6251

    Article  PubMed  CAS  Google Scholar 

  • Thomachot MC et al (2004) Breast carcinoma cells promote the differentiation of CD34+ progenitors towards 2 different subpopulations of dendritic cells with CD1a(high)CD86(−)Langerin- and CD1a(+)CD86(+)Langerin+ phenotypes. Int J Cancer 110(5):710–720

    Article  PubMed  CAS  Google Scholar 

  • Thornton AM, Shevach EM (1998) CD4+ CD25+ immunoregulatory T cells suppress polyclonal T cell activation in vitro by inhibiting interleukin 2 production. J Exp Med 188(2):287–296

    Article  PubMed  CAS  Google Scholar 

  • Tiemessen MM et al (2007) CD4+ CD25+ Foxp3+ regulatory T cells induce alternative activation of human monocytes/macrophages. Proc Natl Acad Sci USA 104(49):19446–19451

    Article  PubMed  CAS  Google Scholar 

  • Ueda Y et al (2004) Overexpression of HER2 (erbB2) in human breast epithelial cells unmasks transforming growth factor beta-induced cell motility. J Biol Chem 279(23):24505–24513

    Article  PubMed  CAS  Google Scholar 

  • Veldhoen M et al (2006a) TGFbeta in the context of an inflammatory cytokine milieu supports de novo differentiation of IL-17-producing T cells. Immunity 24(2):179–189

    Article  PubMed  CAS  Google Scholar 

  • Veldhoen M et al (2006b) Modulation of dendritic cell function by naive and regulatory CD4+ T cells. J Immunol 176(10):6202–6210

    PubMed  CAS  Google Scholar 

  • Wang MT, Honn KV, Nie D (2007) Cyclooxygenases, prostanoids, and tumor progression. Cancer Metastasis Rev 26(3–4):525–534

    Article  PubMed  CAS  Google Scholar 

  • Wei S et al (2005) Plasmacytoid dendritic cells induce CD8+ regulatory T cells in human ovarian carcinoma. Cancer Res 65(12):5020–5026

    Article  PubMed  CAS  Google Scholar 

  • Wei S, Kryczek I, Zou W (2006) Regulatory T-cell compartmentalization and trafficking. Blood 108(2):426–431

    Article  PubMed  CAS  Google Scholar 

  • Welch DR, Fabra A, Nakajima M (1990) Transforming growth factor beta stimulates mammary adenocarcinoma cell invasion and metastatic potential. Proc Natl Acad Sci USA 87(19):7678–7682

    Article  PubMed  CAS  Google Scholar 

  • Wilson NJ et al (2007) Development, cytokine profile and function of human interleukin 17-producing helper T cells. Nat Immunol 8(9):950–957

    Article  PubMed  CAS  Google Scholar 

  • Wolf D et al (2005) The expression of the regulatory T cell-specific forkhead box transcription factor FoxP3 is associated with poor prognosis in ovarian cancer. Clin Cancer Res 11(23):8326–8331

    Article  PubMed  CAS  Google Scholar 

  • Woo EY et al (2001) Regulatory CD4(+)CD25(+) T cells in tumors from patients with early-stage non-small cell lung cancer and late-stage ovarian cancer. Cancer Res 61(12):4766–4772

    PubMed  CAS  Google Scholar 

  • Xiao S et al (2008) Retinoic acid increases Foxp3+ regulatory T cells and inhibits development of Th17 cells by enhancing TGF-beta-driven Smad3 signaling and inhibiting IL-6 and IL-23 receptor expression. J Immunol 181(4):2277–2284

    PubMed  CAS  Google Scholar 

  • Yamamoto M et al (2009) Enhancement of anti-tumor immunity by high levels of Th1 and Th17 with a combination of dendritic cell fusion hybrids and regulatory T cell depletion in pancreatic cancer. Oncol Rep 22(2):337–343

    PubMed  CAS  Google Scholar 

  • Yang L et al (2008a) IL-21 and TGF-beta are required for differentiation of human T(H)17 cells. Nature 454(7202):350–352

    Article  PubMed  CAS  Google Scholar 

  • Yang XO et al (2008b) Molecular antagonism and plasticity of regulatory and inflammatory T cell programs. Immunity 29(1):44–56

    Article  PubMed  CAS  Google Scholar 

  • Yao C et al (2009) Prostaglandin E2-EP4 signaling promotes immune inflammation through Th1 cell differentiation and Th17 cell expansion. Nat Med 15(6):633–640

    Article  PubMed  CAS  Google Scholar 

  • Yen D et al (2006) IL-23 is essential for T cell-mediated colitis and promotes inflammation via IL-17 and IL-6. J Clin Invest 116(5):1310–1316

    Article  PubMed  CAS  Google Scholar 

  • Yu QT et al (2007) Expression and functional characterization of FOXP3+ CD4+ regulatory T cells in ulcerative colitis. Inflamm Bowel Dis 13(2):191–199

    Article  PubMed  Google Scholar 

  • Zhang B et al (2008) The prevalence of Th17 cells in patients with gastric cancer. Biochem Biophys Res Commun 374(3):533–537

    Article  PubMed  CAS  Google Scholar 

  • Zhou L et al (2007) IL-6 programs T(H)-17 cell differentiation by promoting sequential engagement of the IL-21 and IL-23 pathways. Nat Immunol 8(9):967–974

    Article  PubMed  CAS  Google Scholar 

  • Zhou L et al (2008) TGF-beta-induced Foxp3 inhibits T(H)17 cell differentiation by antagonizing RORgammat function. Nature 453(7192):236–240

    Article  PubMed  CAS  Google Scholar 

  • Zou W (2005) Immunosuppressive networks in the tumour environment and their therapeutic relevance. Nat Rev Cancer 5(4):263–274

    Article  PubMed  CAS  Google Scholar 

  • Zou W (2006) Regulatory T cells, tumour immunity and immunotherapy. Nat Rev Immunol 6(4):295–307

    Article  PubMed  CAS  Google Scholar 

  • Zou W, Chen L (2008) Inhibitory B7-family molecules in the tumour microenvironment. Nat Rev Immunol 8(6):467–477

    Article  PubMed  CAS  Google Scholar 

  • Zou L et al (2004) Bone marrow is a reservoir for CD4+ CD25+ regulatory T cells that traffic through CXCL12/CXCR4 signals. Cancer Res 64(22):8451–8455

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Surgery, University of Michigan, Ann Arbor, MI, 48109, USA

    Ilona Kryczek, Ende Zhao, Guobin Wang & Weiping Zou

  2. Department of Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China

    Ke Wu & Ende Zhao

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  1. Ilona Kryczek
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  2. Ke Wu
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  3. Ende Zhao
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  4. Guobin Wang
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  5. Weiping Zou
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Correspondence to Weiping Zou .

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  1. Center for Cell & Gene Therapy, Baylor College of Medicine, Baylor Plaza 1, Houston, 77030, Texas, USA

    Rongfu Wang

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Kryczek, I., Wu, K., Zhao, E., Wang, G., Zou, W. (2012). Relationship Between Th17 and Regulatory T Cells in the Tumor Environment. In: Wang, R. (eds) Innate Immune Regulation and Cancer Immunotherapy. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-9914-6_10

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