γδ T cells in cancer

Silva‐Santos, Bruno; Serre, Karine; Norell, Håkan

doi:10.1038/nri3904

Cited by 469 publications

(486 citation statements)

References 93 publications

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“…Thus, the mechanisms downstream IL-17 produced by gd T cells in the Ret melanoma model are consistent with those reviewed in ref. 2 . Indeed, gd17 cells promote directly, or via cancer cell stimulation, the recruitment, expansion, differentiation and survival of PMN-MDSCs both in mouse models of hepatocellular carcinoma 18 and breast cancer, 17 and in human colorectal cancer.…”

Section: Discussionmentioning

confidence: 99%

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Nitric oxide synthase 2 is involved in the pro-tumorigenic potential of γδ17 T cells in melanoma

et al. 2016

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ABSTRACTgd T lymphocytes may exert either protective or tumor-promoting functions in cancer, mostly based on their polarization toward interferon (IFN)-g or interleukin (IL)-17 productions, respectively. Here, we demonstrate that gd T cells accelerate the spontaneous metastatic melanoma development in a model of transgenic mice for the human RET oncogene (Ret mice). We identify unanticipated roles of inducible nitric oxide synthase (NOS2) in favoring the recruitment of pro-tumor gd T cells within the primary tumor. gd T cells isolated from Ret mice deficient for NOS2 produced more IFNg and less IL-17 than their counterparts from Ret mice. By supporting IL-17 production by gd T cells, NOS2 leads to the recruitment of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) and metastasis formation. NOS2 also reduces the cytotoxicity of gd T cells toward melanoma cells. Finally, we detected NOS2 expressing gd T cells in the primary tumor and tumor-draining lymph nodes in Ret mice, but also in human melanoma. Overall our results support that this NOS2 autocrine expression is responsible for the polarization of gd T cells toward a pro-tumor profile.

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Section: Discussionmentioning

confidence: 99%

“…2 ). Recently, the tumor-associated gd T cell specific signature emerged as the most significant favorable cancer-wide prognostic immune population in a meta-analysis of human malignancies.…”

Section: Introductionmentioning

confidence: 99%

Nitric oxide synthase 2 is involved in the pro-tumorigenic potential of γδ17 T cells in melanoma

et al. 2016

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“…Classical T cells (alpha-beta), unlike gamma-delta T cells (Silva-Santos et al, 2015) and B cells, cannot detect soluble antigen. Instead, they recognize antigen in the form of peptides bound to MHC molecules.…”

Section: Types Of T Cells In Actmentioning

confidence: 99%

“…Other types of T cells that have been investigated for immunotherapy are natural killer T (NKT) cells and gamma delta T cells (γδ Tc) (Fujii et al, 2013;Silva-Santos et al, 2015). NKT cells are a heterogeneous group of T cells that have properties of both natural killer (NK) cells and T cells; they recognize CD1d molecule and constitute only approximately 0.1% of all peripheral blood T cells.…”

Section: Cd4+ T Cells Are Equally Important As Cd8+ Cellsmentioning

confidence: 99%

Adoptive immunotherapy via CD4+ versus CD8+ T cells

Phan-Lai

2016

Biomed Res Ther

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Abstract-The goal of cancer immunotherapy is to induce specific and durable antitumor immunity. Adoptive T cell therapy (ACT) has garnered wide interest, particularly in regard to strategies to improve T cell efficacy in trials. There are many types of T cells (and subsets) which can be selected for use in ACT. CD4+ T cells are critical for the regulation, activation and aid of host defense mechanisms and, importantly, for enhancing the function of tumor-specific CD8+ T cells. To date, much research in cancer immunotherapy has focused on CD8+ T cells, in melanoma and other cancers. Both CD4+ T cells and CD8+ T cells have been evaluated as ACT in mice and humans, and both are effective at eliciting antitumor responses. IL-17 producing CD4+ T cells are a new subset of CD4+ T cells to be evaluated in ACT models. This review discusses the benefits of adoptive immunotherapy mediated by CD8+ and CD4+ cells. It also discusses the various type of T cells, source of T cells, and ex vivo cytokine growth factors for augmenting clinical efficacy of ACT.

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“…These aspects may be translationally relevant and may provide novel therapeutic avenues in anti-tumor immune responses. [11][12][13] …”

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confidence: 99%