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The dichotomy of T helper 17 cells in cancer

Nature Reviews Immunology volume 17, page 592 (2017)Cite this article

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Immunologists have been left with considerable bewilderment by the complexity posed by the brands and flavours of T helper cell subsets. The T helper 17 (TH17) subset is a recent addition and research has focused extensively on basic biology, lineage development, promotion of inflammation and relevance in autoimmunity, with a critical role being identified for TH17 cells in host defence against fungal infections. In their timely and insightful Review article (The dichotomous nature of T helper 17 cells. Nat. Rev. Immunol. http://dx.doi.org/10.1038/nri.2017.50 (2017))1, Stockinger and Omenetti discuss TH17 in non-inflammatory mucosal homeostasis and 'inflammatory' issues surrounding TH17 pathology, and highlight the beneficial and pathogenic aspects of TH17 cells. However, emerging evidence reveals the equally dichotomous nature of the TH17 cell subset in cancer, which the authors do not discuss. Although these cells were initially identified as the mediator of some autoimmune conditions that were previously ascribed to the TH1 cell subset2, their importance in cancer is coming to light. There is now strong evidence to support a role, although dichotomous, for TH17 cells in cancer.

One of the fundamental questions regarding the TH17 cell subset is whether tumour-associated TH17 cells are functional effector T cells with any protective role against cancer. Kryczek et al.3 conducted an extensive study to map the phenotype, mechanism of induction, biological function and clinical relevance of TH17 cells in tumours from patients with ovarian cancer. This study was one of the first to systemically and mechanistically investigate, using multiple complementary strategies, TH17 cells in the human tumour microenvironment. Their study documented the presence of TH17 cells in the tumour microenviroment. TH17 cells infiltrating the tumour were positively associated with effector immune cells, including interferon-γ (IFNγ)-producing effector T cells, CD8+ T cells and natural killer (NK) cells. Moreover, the tumour-associated TH17 cells expressed effector cytokines with a profile resembling that of polyfunctional effector T cells, which is similar to what is observed in patients with infectious disease, and contributed to protective tumour immunity3. In another study, increased numbers of highly differentiated TH17 cells in the prostate correlated with slower progression of prostate cancer4. In murine models, tumour-specific TH17 cells protected against various tumours and promoted tumour-specific cytotoxic T cell responses, whereas IL-17-deficient mice were susceptible to tumour development with impaired CD8+ effector T cell differentiation5,6. The adoptive transfer of IL-17-secreting CD8+ T cells into mice bearing established vascularized B16F10 melanomas also enhanced antitumour immunity, resulting in the regression of established tumours5.

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References

  1. Stockinger, B. & Omenetti, S. The dichotomous nature of T helper 17 cells. Nat. Rev. Immunol. http://dx.doi.org/10.1038/nri.2017.50 (2017).

  2. Langrish, C. L. et al. IL-23 drives a pathogenic T cell population that induces autoimmune inflammation. J. Exp. Med. 201, 233–240 (2005).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  4. Sfanos, K. S. et al. Phenotypic analysis of prostate-infiltrating lymphocytes reveals TH17 and Treg skewing. Clin. Cancer Res. 14, 3254–3261 (2008).

    Article  CAS  Google Scholar 

  5. Hinrichs, C. S. et al. Type 17 CD8+ T cells display enhanced antitumor immunity. Blood 114, 596–599 (2009).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  7. Kulig, P. et al. IL17A-mediated endothelial breach promotes metastasis formation. Cancer Immunol. Res. 4, 26–32 (2016).

    Article  CAS  Google Scholar 

  8. McGeachy, M. J. et al. TGF-beta and IL-6 drive the production of IL-17 and IL-10 by T cells and restrain TH-17 cell-mediated pathology. Nat. Immunol. 8, 1390–1397 (2007).

    Article  CAS  Google Scholar 

  9. Charles, K. A. et al. 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 (2009).

    Article  CAS  Google Scholar 

  10. Langowski, J. L. et al. IL-23 promotes tumour incidence and growth. Nature 442, 461–465 (2006).

    Article  CAS  Google Scholar 

  11. Tosolini, M. et al. Clinical impact of different classes of infiltrating T cytotoxic and helper cells (Th1, th2, treg, th17) in patients with colorectal cancer. Cancer Res. 71, 1263–1271 (2011).

    Article  CAS  Google Scholar 

  12. He, D. et al. IL-17 promotes tumor development through the induction of tumor promoting microenvironments at tumor sites and myeloid-derived suppressor cells. J. Immunol. 184, 2281–2288 (2010).

    Article  CAS  Google Scholar 

  13. Coussens, L. M. & Werb, Z. Inflammation and cancer. Nature 420, 860–867 (2002).

    Article  CAS  Google Scholar 

  14. Lee, Y. K. et al. Late developmental plasticity in the T helper 17 lineage. Immunity 30, 92–107 (2009).

    Article  CAS  Google Scholar 

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  1. Lekh N. Dahal is at the Antibody and Vaccine Group, Cancer Sciences Unit, Faculty of Medicine, University of Southampton, Southampton General Hospital, Southampton SO16 6YD, UK.,

    Lekh N. Dahal

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Dahal, L. The dichotomy of T helper 17 cells in cancer. Nat Rev Immunol 17, 592 (2017). https://doi.org/10.1038/nri.2017.93

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