Tumor‐infiltrating IL‐17‐producing γδ T cells support the progression of tumor by promoting angiogenesis

D Wakita, K Sumida, Y Iwakura… - European journal of …, 2010 - Wiley Online Library
D Wakita, K Sumida, Y Iwakura, H Nishikawa, T Ohkuri, K Chamoto, H Kitamura…
European journal of immunology, 2010Wiley Online Library
Based on the evidence that IL‐17 is a key cytokine involved in various inflammatory
diseases, we explored the critical role of IL‐17‐producing γδ T cells for tumor development
in tumor‐bearing mouse model. IL‐17−/− mice exhibited a significant reduction of tumor
growth, concomitantly with the decrease of vascular density at lesion area, indicating a pro‐
tumor property of IL‐17. Among tumor‐infiltrating lymphocytes (TIL), γδ T cells were the
major cellular source of IL‐17. Analysis of TCR repertoires in TIL‐γδ T cells showed that …
Abstract
Based on the evidence that IL‐17 is a key cytokine involved in various inflammatory diseases, we explored the critical role of IL‐17‐producing γδ T cells for tumor development in tumor‐bearing mouse model. IL‐17−/− mice exhibited a significant reduction of tumor growth, concomitantly with the decrease of vascular density at lesion area, indicating a pro‐tumor property of IL‐17. Among tumor‐infiltrating lymphocytes (TIL), γδ T cells were the major cellular source of IL‐17. Analysis of TCR repertoires in TIL‐γδ T cells showed that circulating γδ T cells, but not skin resident Vγ5+γδ T cells, produced IL‐17. Neutralizing antibodies against IL‐23, IL‐6, and TGF‐β, which were produced within the tumor microenvironment, inhibited the induction of IL‐17‐producing γδ T cells. IL‐17 production by tumor‐infiltrating γδ T cells was blocked by anti‐γδTCR or anti‐NKG2D antibodies, indicating that these ligands, expressed within the tumor microenvironment, are involved in γδ T‐cell activation. The IL‐17‐producing TIL‐γδ T cells exhibited reduced levels of perforin mRNA expression, but increased levels of COX‐2 mRNA expression. Together, our findings support the novel concept that IL‐17‐producing γδ T cells, generated in response to tumor microenvironment, act as tumor‐promoting cells by inducing angiogenesis.
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