Skip to main content
SpringerLink
Log in
SpringerLink
Log in

TH17 Cells in the Tumor Micro-environment

  • Chapter
  • First Online:
TH17 Cells in Health and Disease

Abstract

Although it has been established that TH17 cells play pivotal roles in the development and pathogenesis of many auto-immune diseases, their function in cancer is not yet as well-defined. Current research has documented both pro and anti-tumor roles for TH17 cells or more precisely, TH17-associated cytokines. Here we will examine those functions, as well as population kinetics, phenotype, and sources of TH17 cells within the tumor micro-environment.

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 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
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

  • Acosta-Rodriguez, E.V., Napolitani, G., Lanzavecchia, A., and Sallusto, F. (2007). 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, 942–949.

    Article  PubMed  CAS  Google Scholar 

  • Almeida, J.R., Price, D.A., Papagno, L., Arkoub, Z.A., Sauce, D., Bornstein, E., Asher, T.E., Samri, A., Schnuriger, A., Theodorou, I., 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, 2473–2485.

    Article  PubMed  CAS  Google Scholar 

  • Angiolillo, A.L., Sgadari, C., Taub, D.D., Liao, F., Farber, J.M., Maheshwari, S., Kleinman, H.K., Reaman, G.H., and Tosato, G. (1995). Human interferon-inducible protein 10 is a potent inhibitor of angiogenesis in vivo. J Exp Med 182, 155–162.

    Article  PubMed  CAS  Google Scholar 

  • Annunziato, F., Cosmi, L., Santarlasci, V., Maggi, L., Liotta, F., Mazzinghi, B., Parente, E., Fili, L., Ferri, S., Frosali, F., et al. (2007). Phenotypic and functional features of human Th17 cells. J Exp Med 204, 1849–1861.

    Article  PubMed  CAS  Google Scholar 

  • Arens, R., Wang, P., Sidney, J., Loewendorf, A., Sette, A., Schoenberger, S.P., Peters, B., and Benedict, C.A. (2008). Cutting edge: murine cytomegalovirus induces a polyfunctional CD4 T cell response. J Immunol 180, 6472–6476.

    PubMed  CAS  Google Scholar 

  • Bell, D., Chomarat, P., Broyles, D., Netto, G., Harb, G.M., Lebecque, S., Valladeau, J., Davoust, J., Palucka, K.A., and Banchereau, J. (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, 1417–1426.

    Article  PubMed  CAS  Google Scholar 

  • Benchetrit, F., Ciree, A., Vives, V., Warnier, G., Gey, A., Sautes-Fridman, C., Fossiez, F., Haicheur, N., Fridman, W.H., and Tartour, E. (2002). Interleukin-17 inhibits tumor cell growth by means of a T-cell-dependent mechanism. Blood 99, 2114–2121.

    Article  PubMed  CAS  Google Scholar 

  • Bending, D., De La Pena, H., Veldhoen, M., Phillips, J.M., Uyttenhove, C., Stockinger, B., and Cooke, A. (2009). Highly purified Th17 cells from BDC2.5NOD mice convert into Th1-like cells in NOD/SCID recipient mice. J Clin Invest 119, 565–572.

    Google Scholar 

  • Beriou, G., Costantino, C.M., Ashley, C.W., Yang, L., Kuchroo, V.K., Baecher-Allan, C., and Hafler, D.A. (2009). IL-17-producing human peripheral regulatory T cells retain suppressive function. Blood 113, 4240–4249.

    Article  PubMed  CAS  Google Scholar 

  • Bettelli, E., Carrier, Y., Gao, W., Korn, T., Strom, T.B., Oukka, M., Weiner, H.L., and Kuchroo, V.K. (2006). Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells. Nature 441, 235–238.

    Article  PubMed  CAS  Google Scholar 

  • Bleul, C.C., Fuhlbrigge, R.C., Casasnovas, J.M., Aiuti, A., and Springer, T.A. (1996). A highly efficacious lymphocyte chemo-attractant, stromal cell-derived factor 1 (SDF-1). J Exp Med 184, 1101–1109.

    Article  PubMed  CAS  Google Scholar 

  • Borsellino, G., Kleinewietfeld, M., Di Mitri, D., Sternjak, A., Diamantini, A., Giometto, R., Hopner, S., Centonze, D., Bernardi, G., Dell’Acqua, M.L., et al. (2007). Expression of ectonucleotidase CD39 by Foxp3+ Treg cells: hydrolysis of extracellular ATP and immune suppression. Blood 110, 1225–1232.

    Article  PubMed  CAS  Google Scholar 

  • Bronte, V. (2008). Th17 and cancer: friends or foes? Blood 112, 214.

    Article  PubMed  CAS  Google Scholar 

  • Carr, M.W., Roth, S.J., Luther, E., Rose, S.S., and Springer, T.A. (1994). Monocyte chemo-attractant protein 1 acts as a T-lymphocyte chemo-attractant. Proc Natl Acad Sci USA 91, 3652–3656.

    Article  PubMed  CAS  Google Scholar 

  • Charles, K.A., Kulbe, H., Soper, R., Escorcio-Correia, M., Lawrence, T., Schultheis, A., Chakravarty, P., Thompson, R.G., Kollias, G., Smyth, J.F., et al. (2009). The tumor-promoting actions of TNF-alpha involve TNFR1 and IL-17 in ovarian cancer in mice and humans. J Clin Invest 119, 3011–3023.

    Article  PubMed  CAS  Google Scholar 

  • Chaudhry, A., Rudra, D., Treuting, P., Samstein, R.M., Liang, Y., Kas, A., and Rudensky, A.Y. (2009). CD4+ regulatory T cells control TH17 responses in a Stat3-dependent manner. Science 326, 986–991.

    Article  PubMed  CAS  Google Scholar 

  • Chen, X., Wan, J., Liu, J., Xie, W., Diao, X., Xu, J., Zhu, B., and Chen, Z. (2009). Increased IL17-producing cells correlate with poor survival and lymphangiogenesis in NSCLC patients. Lung Cancer 69, 348–354.

    Google Scholar 

  • Chung, Y., Chang, S.H., Martinez, G.J., Yang, X.O., Nurieva, R., Kang, H.S., Ma, L., Watowich, S.S., Jetten, A.M., Tian, Q., and Dong, C. (2009). Critical regulation of early Th17 cell differentiation by interleukin-1 signaling. Immunity 30, 576–587.

    Article  PubMed  CAS  Google Scholar 

  • Cosmi, L., De Palma, R., Santarlasci, V., Maggi, L., Capone, M., Frosali, F., Rodolico, G., Querci, V., Abbate, G., Angeli, R., et al. (2008). Human interleukin 17-producing cells originate from a CD161+CD4+ T cell precursor. J Exp Med 205, 1903–1916.

    Article  PubMed  CAS  Google Scholar 

  • Curiel, T.J., Coukos, G., Zou, L., Alvarez, X., Cheng, P., Mottram, P., Evdemon-Hogan, M., Conejo-Garcia, J.R., Zhang, L., Burow, M., et al. (2004). Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nat Med 10, 942–949.

    Article  PubMed  CAS  Google Scholar 

  • Deaglio, S., Dwyer, K.M., Gao, W., Friedman, D., Usheva, A., Erat, A., Chen, J.F., Enjyoji, K., Linden, J., Oukka, M., et al. (2007). Adenosine generation catalyzed by CD39 and CD73 expressed on regulatory T cells mediates immune suppression. J Exp Med 204, 1257–1265.

    Article  PubMed  CAS  Google Scholar 

  • Deknuydt, F., Bioley, G., Valmori, D., and Ayyoub, M. (2009). IL-1beta and IL-2 convert human Treg into T (H) 17 cells. Clin Immunol 131, 298–307.

    Article  PubMed  CAS  Google Scholar 

  • Derhovanessian, E., Adams, V., Hahnel, K., Groeger, A., Pandha, H., Ward, S., and Pawelec, G. (2009). Pretreatment frequency of circulating IL-17+ CD4+ T-cells, but not Tregs, correlates with clinical response to whole-cell vaccination in prostate cancer patients. Int J Cancer 125, 1372–1379.

    Article  PubMed  CAS  Google Scholar 

  • Dhodapkar, K.M., Barbuto, S., Matthews, P., Kukreja, A., Mazumder, A., Vesole, D., Jagannath, S., and Dhodapkar, M.V. (2008). Dendritic cells mediate the induction of polyfunctional human IL17-producing cells (Th17-1 cells) enriched in the bone marrow of patients with myeloma. Blood 112, 2878–2885.

    Article  PubMed  CAS  Google Scholar 

  • Dufour, J.H., Dziejman, M., Liu, M.T., Leung, J.H., Lane, T.E., and Luster, A.D. (2002). IFNgamma-inducible protein 10 (IP-10; CXCL10)-deficient mice reveal a role for IP-10 in effector T cell generation and trafficking. J Immunol 168, 3195–3204.

    PubMed  CAS  Google Scholar 

  • Enarsson, K., Lundgren, A., Kindlund, B., Hermansson, M., Roncador, G., Banham, A.H., Lundin, B.S., and Quiding-Jarbrink, M. (2006). Function and recruitment of mucosal regulatory T cells in human chronic Helicobacter pylori infection and gastric adenocarcinoma. Clin Immunol 121, 358–368.

    Article  PubMed  CAS  Google Scholar 

  • Galon, J., Costes, A., Sanchez-Cabo, F., Kirilovsky, A., Mlecnik, B., Lagorce-Pages, C., Tosolini, M., Camus, M., Berger, A., Wind, P., et al. (2006). Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Science 313, 1960–1964.

    Article  PubMed  CAS  Google Scholar 

  • Gulen, M.F., Kang, Z., Bulek, K., Youzhong, W., Kim, T.W., Chen, Y., Altuntas, C.Z., Sass Bak-Jensen, K., McGeachy, M.J., Do, J.S., et al. (2010). The Receptor SIGIRR Suppresses Th17 Cell Proliferation via Inhibition of the Interleukin-1 Receptor Pathway and mTOR Kinase Activation. Immunity 32, 54–66.

    Article  PubMed  CAS  Google Scholar 

  • Harrington, L.E., Hatton, R.D., Mangan, P.R., Turner, H., Murphy, T.L., Murphy, K.M., and Weaver, C.T. (2005). Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages. Nat Immunol 6, 1123–1132.

    Article  PubMed  CAS  Google Scholar 

  • He, D., Li, H., Yusuf, N., Elmets, C.A., Li, J., Mountz, J.D., and Xu, H. (2010). IL-17 promotes tumor development through the induction of tumor promoting micro-environments at tumor sites and myeloid-derived suppressor cells. J Immunol 184, 2281–2288.

    Article  PubMed  CAS  Google Scholar 

  • Hieshima, K., Imai, T., Opdenakker, G., Van Damme, J., Kusuda, J., Tei, H., Sakaki, Y., Takatsuki, K., Miura, R., Yoshie, O., and Nomiyama, H. (1997). Molecular cloning of a novel human CC chemokine liver and activation-regulated chemokine (LARC) expressed in liver. Chemotactic activity for lymphocytes and gene localization on chromosome 2. J Biol Chem 272, 5846–5853.

    Article  PubMed  CAS  Google Scholar 

  • Hinrichs, C.S., Kaiser, A., Paulos, C.M., Cassard, L., Sanchez-Perez, L., Heemskerk, B., Wrzesinski, C., Borman, Z.A., Muranski, P., and Restifo, N.P. (2009). Type 17 CD8+ T cells display enhanced antitumor immunity. Blood 114, 596–599.

    Article  PubMed  CAS  Google Scholar 

  • Hirahara, N., Nio, Y., Sasaki, S., Minari, Y., Takamura, M., Iguchi, C., Dong, M., Yamasawa, K., and Tamura, K. (2001). Inoculation of human interleukin-17 gene-transfected Meth-A fibrosarcoma cells induces T cell-dependent tumor-specific immunity in mice. Oncology 61, 79–89.

    Article  PubMed  CAS  Google Scholar 

  • Hirota, K., Yoshitomi, H., Hashimoto, M., Maeda, S., Teradaira, S., Sugimoto, N., Yamaguchi, T., Nomura, T., Ito, H., Nakamura, T., et al. (2007). Preferential recruitment of CCR6expressing Th17 cells to inflamed joints via CCL20 in rheumatoid arthritis and its animal model. J Exp Med 204, 2803–2812.

    Article  PubMed  CAS  Google Scholar 

  • Honorati, M.C., Neri, S., Cattini, L., and Facchini, A. (2006). Interleukin-17, a regulator of angiogenic factor release by synovial fibroblasts. Osteoarthritis Cartilage 14, 345–352.

    Article  PubMed  CAS  Google Scholar 

  • Horlock, C., Stott, B., Dyson, P.J., Morishita, M., Coombes, R.C., Savage, P., and Stebbing, J. (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, 1061–1067.

    Article  PubMed  CAS  Google Scholar 

  • Hu, J., Yuan, X., Belladonna, M.L., Ong, J.M., Wachsmann-Hogiu, S., Farkas, D.L., Black, K.L., and Yu, J.S. (2006). Induction of potent antitumor immunity by intra-tumoral injection of interleukin 23-transduced dendritic cells. Cancer Res 66, 8887–8896.

    Article  PubMed  CAS  Google Scholar 

  • Inozume, T., Hanada, K., Wang, Q.J., and Yang, J.C. (2009). IL-17 secreted by tumor reactive T cells induces IL-8 release by human renal cancer cells. J Immunother 32, 109–117.

    Article  PubMed  CAS  Google Scholar 

  • Kaiga, T., Sato, M., Kaneda, H., Iwakura, Y., Takayama, T., and Tahara, H. (2007). Systemic administration of IL-23 induces potent antitumor immunity primarily mediated through Th1-type response in association with the endogenously expressed IL-12. J Immunol 178, 7571–7580.

    PubMed  CAS  Google Scholar 

  • Kao, J.Y., Zhang, M., Miller, M.J., Mills, J.C., Wang, B., Liu, M., Eaton, K.A., Zou, W., Berndt, B.E., Cole, T.S., et al. (2009). Helicobacter pylori Immune Escape Is Mediated by Dendritic Cell-Induced Treg Skewing and Th17 Suppression in Mice. Gastroenterology 138, 1046–1054.

    Google Scholar 

  • Kimura, A., Naka, T., and 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, 12099–12104.

    Article  PubMed  CAS  Google Scholar 

  • Kleinschek, M.A., Boniface, K., Sadekova, S., Grein, J., Murphy, E.E., Turner, S.P., Raskin, L., Desai, B., Faubion, W.A., de Waal Malefyt, R., et al. (2009). Circulating and gut-resident human Th17 cells express CD161 and promote intestinal inflammation. J Exp Med 206, 525–534.

    Article  PubMed  CAS  Google Scholar 

  • Kottke, T., Sanchez-Perez, L., Diaz, R.M., Thompson, J., Chong, H., Harrington, K., Calderwood, S.K., Pulido, J., Georgopoulos, N., Selby, P., et al. (2007). Induction of hsp70-mediated Th17 autoimmunity can be exploited as immunotherapy for metastatic prostate cancer. Cancer Res 67, 11970–11979.

    Article  PubMed  CAS  Google Scholar 

  • Koyama, K., Kagamu, H., Miura, S., Hiura, T., Miyabayashi, T., Itoh, R., Kuriyama, H., Tanaka, H., Tanaka, J., Yoshizawa, H., 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, 6770–6779.

    Article  PubMed  CAS  Google Scholar 

  • Kryczek, I., Banerjee, M., Cheng, P., Vatan, L., Szeliga, W., Wei, S., Huang, E., Finlayson, E., Simeone, D., Welling, T.H., et al. (2009a). Phenotype, distribution, generation, and functional and clinical relevance of Th17 cells in the human tumor environments. Blood 114, 1141–1149.

    Article  PubMed  CAS  Google Scholar 

  • Kryczek, I., Bruce, A.T., Gudjonsson, J.E., Johnston, A., Aphale, A., Vatan, L., Szeliga, W., Wang, Y., Liu, Y., Welling, T.H., et al. (2008a). Induction of IL-17+ T cell trafficking and development by IFN-gamma: mechanism and pathological relevance in psoriasis. J Immunol 181, 4733–4741.

    PubMed  CAS  Google Scholar 

  • Kryczek, I., Grybos, M., Karabon, L., Klimczak, A., and Lange, A. (2000). IL-6 production in ovarian carcinoma is associated with histiotype and biological characteristics of the tumour and influences local immunity. Br J Cancer 82, 621–628.

    Article  PubMed  CAS  Google Scholar 

  • Kryczek, I., Lange, A., Mottram, P., Alvarez, X., Cheng, P., Hogan, M., Moons, L., Wei, S., Zou, L., Machelon, V., et al. (2005). CXCL12 and vascular endothelial growth factor synergistically induce neoangiogenesis in human ovarian cancers. Cancer Res 65, 465–472

    PubMed  CAS  Google Scholar 

  • Kryczek, I., Wei, S., Gong, W., Shu, X., Szeliga, W., Vatan, L., Chen, L., Wang, G., and Zou, W. (2008b). Cutting edge: IFN-gamma enables APC to promote memory Th17 and abate Th1 cell development. J Immunol 181, 5842–5846.

    Google Scholar 

  • Kryczek, I., Wei, S., Szeliga, W., Vatan, L., and Zou, W. (2009b). Endogenous IL-17 contributes to reduced tumor growth and metastasis. Blood 114, 357–359.

    Google Scholar 

  • Kryczek, I., Wei, S., Vatan, L., Escara-Wilke, J., Szeliga, W., Keller, E.T., and Zou, W. (2007a). 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, 1423–1426.

    PubMed  CAS  Google Scholar 

  • Kryczek, I., Wei, S., Zou, L., Altuwaijri, S., Szeliga, W., Kolls, J., Chang, A., and Zou, W. (2007b). Cutting edge: Th17 and regulatory T cell dynamics and the regulation by IL2 in the tumor micro-environment. J Immunol 178, 6730–6733.

    PubMed  CAS  Google Scholar 

  • Kryczek, I., Zou, L., Rodriguez, P., Zhu, G., Wei, S., Mottram, P., Brumlik, M., Cheng, P., Curiel, T., Myers, L., et al. (2006). B7-H4 expression identifies a novel suppressive macrophage population in human ovarian carcinoma. J Exp Med 203, 871–881.

    Article  PubMed  CAS  Google Scholar 

  • Langowski, J.L., Kastelein, R.A., and Oft, M. (2007). Swords into plowshares: IL-23 repurposes tumor immune surveillance. Trends Immunol 28, 207–212.

    Article  PubMed  CAS  Google Scholar 

  • Langowski, J.L., Zhang, X., Wu, L., Mattson, J.D., Chen, T., Smith, K., Basham, B., McClanahan, T., Kastelein, R.A., and Oft, M. (2006). IL-23 promotes tumour incidence and growth. Nature 442, 461–465.

    Article  PubMed  CAS  Google Scholar 

  • Lee, Y.K., Turner, H., Maynard, C.L., Oliver, J.R., Chen, D., Elson, C.O., and Weaver, C.T. (2009). Late developmental plasticity in the T helper 17 lineage. Immunity 30, 92–107.

    Article  PubMed  CAS  Google Scholar 

  • Liu, H., and Rohowsky-Kochan, C. (2008). Regulation of IL-17 in human CCR6+ effector memory T cells. J Immunol 180, 7948–7957.

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Martin-Orozco, N., Chung, Y., Chang, S.H., Wang, Y.H., and Dong, C. (2009a). Th17 cells promote pancreatic inflammation but only induce diabetes efficiently in lymphopenic hosts after conversion into Th1 cells. Eur J Immunol 39, 216–224.

    Article  PubMed  CAS  Google Scholar 

  • Martin-Orozco, N., Muranski, P., Chung, Y., Yang, X.O., Yamazaki, T., Lu, S., Hwu, P., Restifo, N.P., Overwijk, W.W., and Dong, C. (2009b). T helper 17 cells promote cytotoxic T cell activation in tumor immunity. Immunity 31, 787–798.

    Article  PubMed  CAS  Google Scholar 

  • Miyahara, Y., Odunsi, K., Chen, W., Peng, G., Matsuzaki, J., and Wang, R.F. (2008). Generation and regulation of human CD4+ IL-17-producing T cells in ovarian cancer. Proc Natl Acad Sci USA 105, 15505–15510.

    Article  PubMed  CAS  Google Scholar 

  • Mucida, D., Park, Y., Kim, G., Turovskaya, O., Scott, I., Kronenberg, M., and Cheroutre, H. (2007). Reciprocal TH17 and regulatory T cell differentiation mediated by retinoic acid. Science 317, 256–260.

    Article  PubMed  CAS  Google Scholar 

  • Munn, D.H. (2009). Th17 cells in ovarian cancer. Blood 114, 1134–1135.

    Article  PubMed  CAS  Google Scholar 

  • Muranski, P., Boni, A., Antony, P.A., Cassard, L., Irvine, K.R., Kaiser, A., Paulos, C.M., Palmer, D.C., Touloukian, C.E., Ptak, K., et al. (2008). Tumor-specific Th17-polarized cells eradicate large established melanoma. Blood 112, 362–373.

    Article  PubMed  CAS  Google Scholar 

  • Muranski, P., and Restifo, N.P. (2009a). Adoptive immunotherapy of cancer using CD4 (+) T cells. Curr Opin Immunol 21, 200–208.

    Article  PubMed  CAS  Google Scholar 

  • Muranski, P., and Restifo, N.P. (2009b). Does IL-17 promote tumor growth? Blood 114, 231–232

    Article  PubMed  CAS  Google Scholar 

  • Murugaiyan, G., and Saha, B. (2009). Protumor vs antitumor functions of IL-17. J Immunol 183, 4169–4175.

    Article  PubMed  CAS  Google Scholar 

  • Nam, J.S., Terabe, M., Kang, M.J., Chae, H., Voong, N., Yang, Y.A., Laurence, A., Michalowska, A., Mamura, M., Lonning, S., et al. (2008). Transforming growth factor beta subverts the immune system into directly promoting tumor growth through interleukin-17. Cancer Res 68, 3915–3923.

    Article  PubMed  CAS  Google Scholar 

  • Numasaki, M., Fukushi, J., Ono, M., Narula, S.K., Zavodny, P.J., Kudo, T., Robbins, P.D., Tahara, H., and Lotze, M.T. (2003). Interleukin-17 promotes angiogenesis and tumor growth. Blood 101, 2620–2627.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Numasaki, M., Watanabe, M., Suzuki, T., Takahashi, H., Nakamura, A., McAllister, F., Hishinuma, T., Goto, J., Lotze, M.T., Kolls, J.K., and Sasaki, H. (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, 6177–6189.

    PubMed  CAS  Google Scholar 

  • Nurieva, R., Yang, X.O., Chung, Y., and Dong, C. (2009). Cutting edge: in vitro generated Th17 cells maintain their cytokine expression program in normal but not lymphopenic hosts. J Immunol 182, 2565–2568.

    Article  PubMed  CAS  Google Scholar 

  • Ohta, A., Gorelik, E., Prasad, S.J., Ronchese, F., Lukashev, D., Wong, M.K., Huang, X., Caldwell, S., Liu, K., Smith, P., et al. (2006). A2A adenosine receptor protects tumors from antitumor T cells. Proc Natl Acad Sci USA 103, 13132–13137.

    Article  PubMed  CAS  Google Scholar 

  • Ohta, A., and Sitkovsky, M. (2001). Role of G-protein-coupled adenosine receptors in downregulation of inflammation and protection from tissue damage. Nature 414, 916–920.

    Article  PubMed  CAS  Google Scholar 

  • Oniki, S., Nagai, H., Horikawa, T., Furukawa, J., Belladonna, M.L., Yoshimoto, T., Hara, I., and Nishigori, C. (2006). Interleukin-23 and interleukin-27 exert quite different antitumor and vaccine effects on poorly immunogenic melanoma. Cancer Res 66, 6395–6404.

    Article  PubMed  CAS  Google Scholar 

  • Overwijk, W.W., de Visser, K.E., Tirion, F.H., de Jong, L.A., Pols, T.W., van der Velden, Y.U., van den Boorn, J.G., Keller, A.M., Buurman, W.A., Theoret, M.R., et al. (2006). Immunological and antitumor effects of IL-23 as a cancer vaccine adjuvant. J Immunol 176, 5213–5222.

    PubMed  CAS  Google Scholar 

  • Pellegrini, M., Calzascia, T., Elford, A.R., Shahinian, A., Lin, A.E., Dissanayake, D., Dhanji, S., Nguyen, L.T., Gronski, M.A., Morre, M., et al. (2009). Adjuvant IL-7 antagonizes multiple cellular and molecular inhibitory networks to enhance immunotherapies. Nat Med 15, 528–536.

    Article  PubMed  CAS  Google Scholar 

  • Precopio, M.L., Betts, M.R., Parrino, J., Price, D.A., Gostick, E., Ambrozak, D.R., Asher, T.E., Douek, D.C., Harari, A., Pantaleo, G., et al. (2007). Immunization with vaccinia virus induces polyfunctional and phenotypically distinctive CD8 (+) T cell responses. J Exp Med 204, 1405–1416.

    Article  PubMed  CAS  Google Scholar 

  • Sato, E., Olson, S.H., Ahn, J., Bundy, B., Nishikawa, H., Qian, F., Jungbluth, A.A., Frosina, D., Gnjatic, S., Ambrosone, C., 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, 18538–18543.

    Article  PubMed  CAS  Google Scholar 

  • Schafer, M., and Werner, S. (2008). Cancer as an overhealing wound: an old hypothesis revisited. Nat Rev Mol Cell Biol 9, 628–638.

    Article  PubMed  CAS  Google Scholar 

  • Sfanos, K.S., Bruno, T.C., Maris, C.H., Xu, L., Thoburn, C.J., DeMarzo, A.M., Meeker, A.K., Isaacs, W.B., and Drake, C.G. (2008). Phenotypic analysis of prostate-infiltrating lymphocytes reveals TH17 and Treg skewing. Clin Cancer Res 14, 3254–3261.

    Article  PubMed  CAS  Google Scholar 

  • Sharma, M.D., Hou, D.Y., Liu, Y., Koni, P.A., Metz, R., Chandler, P., Mellor, A.L., He, Y., and Munn, D.H. (2009). Indoleamine 2, 3-dioxygenase controls conversion of Foxp3+ Tregs to TH17-like cells in tumor-draining lymph nodes. Blood 113, 6102–6111.

    Article  PubMed  CAS  Google Scholar 

  • Su, X., Ye, J., Hsueh, E.C., Zhang, Y., Hoft, D.F., and Peng, G. (2010). Tumor micro-environments direct the recruitment and expansion of human Th17 cells. J Immunol 184, 1630–1641.

    Article  PubMed  CAS  Google Scholar 

  • Sutton, C., Brereton, C., Keogh, B., Mills, K.H., and Lavelle, E.C. (2006). A crucial role for interleukin (IL)-1 in the induction of IL-17-producing T cells that mediate auto-immune encephalomyelitis. J Exp Med 203, 1685–1691.

    Article  PubMed  CAS  Google Scholar 

  • Takahashi, H., Numasaki, M., Lotze, M.T., and Sasaki, H. (2005). Interleukin-17 enhances bFGF-, HGF- and VEGF-induced growth of vascular endothelial cells. Immunol Lett 98, 189–193.

    Article  PubMed  CAS  Google Scholar 

  • Tartour, E., Fossiez, F., Joyeux, I., Galinha, A., Gey, A., Claret, E., Sastre-Garau, X., Couturier, J., Mosseri, V., Vives, V., et al. (1999). Interleukin 17, a T-cell-derived cytokine, promotes tumorigenicity of human cervical tumors in nude mice. Cancer Res 59, 3698–3704.

    PubMed  CAS  Google Scholar 

  • von Euw, E., Chodon, T., Attar, N., Jalil, J., Koya, R.C., Comin-Anduix, B., and Ribas, A. (2009). CTLA4 blockade increases Th17 cells in patients with metastatic melanoma. J Transl Med 7, 35.

    Article  Google Scholar 

  • Voo, K.S., Wang, Y.H., Santori, F.R., Boggiano, C., Arima, K., Bover, L., Hanabuchi, S., Khalili, J., Marinova, E., Zheng, B., et al. (2009). Identification of IL-17-producing FOXP3+ regulatory T cells in humans. Proc Natl Acad Sci USA 106, 4793–4798.

    Article  PubMed  CAS  Google Scholar 

  • Wang, L., Yi, T., Kortylewski, M., Pardoll, D.M., Zeng, D., and Yu, H. (2009). IL-17 can promote tumor growth through an IL-6-Stat3 signaling pathway. J Exp Med 206, 1457–1464.

    Article  PubMed  CAS  Google Scholar 

  • Wilson, N.J., Boniface, K., Chan, J.R., McKenzie, B.S., Blumenschein, W.M., Mattson, J.D., Basham, B., Smith, K., Chen, T., Morel, F., et al. (2007). Development, cytokine profile and function of human interleukin 17-producing helper T cells. Nat Immunol 8, 950–957.

    Article  PubMed  CAS  Google Scholar 

  • Wu, S., Rhee, K.J., Albesiano, E., Rabizadeh, S., Wu, X., Yen, H.R., Huso, D.L., Brancati, F.L., Wick, E., McAllister, F., et al. (2009). A human colonic commensal promotes colon tumorigenesis via activation of T helper type 17 T cell responses. Nat Med 15, 10161022.

    Google Scholar 

  • Xu, L.L., Warren, M.K., Rose, W.L., Gong, W., and Wang, J.M. (1996). Human recombinant monocyte chemotactic protein and other C-C chemokines bind and induce directional migration of dendritic cells in vitro. J Leukoc Biol 60, 365–371.

    PubMed  CAS  Google Scholar 

  • Yamazaki, T., Yang, X.O., Chung, Y., Fukunaga, A., Nurieva, R., Pappu, B., Martin-Orozco, N., Kang, H.S., Ma, L., Panopoulos, A.D., et al. (2008). CCR6 regulates the migration of inflammatory and regulatory T cells. J Immunol 181, 8391–8401.

    PubMed  CAS  Google Scholar 

  • Yang, L., Anderson, D.E., Baecher-Allan, C., Hastings, W.D., Bettelli, E., Oukka, M., Kuchroo, V.K., and Hafler, D.A. (2008). IL-21 and TGF-beta are required for differentiation of human T(H)17 cells. Nature 454, 350–352.

    Article  PubMed  CAS  Google Scholar 

  • Yang, Z.Z., Novak, A.J., Ziesmer, S.C., Witzig, T.E., and Ansell, S.M. (2009). Malignant B cells skew the balance of regulatory T cells and TH17 cells in B-cell non-Hodgkin’s lymphoma. Cancer Res 69, 5522–5530.

    Article  PubMed  CAS  Google Scholar 

  • Yen, H.R., Harris, T.J., Wada, S., Grosso, J.F., Getnet, D., Goldberg, M.V., Liang, K.L., Bruno, T.C., Pyle, K.J., Chan, S.L., et al. (2009). Tc17 CD8 T cells: functional plasticity and subset diversity. J Immunol 183, 7161–7168.

    Article  PubMed  CAS  Google Scholar 

  • Yu, H., Kortylewski, M., and Pardoll, D. (2007). Crosstalk between cancer and immune cells: role of STAT3 in the tumour micro-environment. Nat Rev Immunol 7, 41–51.

    Article  PubMed  CAS  Google Scholar 

  • Yuan, X., Hu, J., Belladonna, M.L., Black, K.L., and Yu, J.S. (2006). Interleukin-23-expressing bone marrow-derived neural stem-like cells exhibit antitumor activity against intracranial glioma. Cancer Res 66, 2630–2638.

    Article  PubMed  CAS  Google Scholar 

  • Zhang, B., Rong, G., Wei, H., Zhang, M., Bi, J., Ma, L., Xue, X., Wei, G., Liu, X., and Fang, G. (2008). The prevalence of Th17 cells in patients with gastric cancer. Biochem Biophys Res Commun 374, 533–537.

    Article  PubMed  CAS  Google Scholar 

  • Zhang, J.P., Yan, J., Xu, J., Pang, X.H., Chen, M.S., Li, L., Wu, C., Li, S.P., and Zheng, L. (2009). Increased intra-tumoral IL-17-producing cells correlate with poor survival in hepatocellular carcinoma patients. J Hepatol 50, 980–989.

    Article  PubMed  CAS  Google Scholar 

  • Zhang, L., Conejo-Garcia, J.R., Katsaros, D., Gimotty, P.A., Massobrio, M., Regnani, G., Makrigiannakis, A., Gray, H., Schlienger, K., Liebman, M.N., et al. (2003). Intra-tumoral T cells, recurrence, and survival in epithelial ovarian cancer. N Engl J Med 348, 203–213.

    Article  PubMed  CAS  Google Scholar 

  • Zheng, H., Fu, G., Dai, T., and Huang, H. (2007). Migration of endothelial progenitor cells mediated by stromal cell-derived factor-1alpha/CXCR4 via PI3K/Akt/eNOS signal transduction pathway. J Cardiovasc Pharmacol 50, 274–280.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Zou, W., Machelon, V., Coulomb-L’Hermin, A., Borvak, J., Nome, F., Isaeva, T., Wei, S., Krzysiek, R., Durand-Gasselin, I., Gordon, A., et al. (2001). Stromal-derived factor-1 in human tumors recruits and alters the function of plasmacytoid precursor dendritic cells. Nat Med 7, 1339–1346.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Surgery, School of Medicine, University of Michigan, C560B MSRB II, 1150 W. Medical Center Dr., Ann Arbor, MI, 48109-0669, USA

    Weiping Zou

Authors
  1. Cailin Moira Wilke
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Weiping Zou
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Weiping Zou .

Editor information

Editors and Affiliations

  1. King's College London, Department of Nephrology and Transplanta, Guy's Hospital, London, WC2R 2LS, United Kingdom

    Shuiping Jiang

Rights and permissions

Reprints and permissions

Copyright information

© 2011 Springer Science+Business Media, LLC

About this chapter

Cite this chapter

Wilke, C.M., Zou, W. (2011). TH17 Cells in the Tumor Micro-environment. In: Jiang, S. (eds) TH17 Cells in Health and Disease. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-9371-7_26

Download citation

Publish with us

Policies and ethics

Search

Navigation