<scp>IL</scp>‐17A‐producing <scp>CD</scp>30<sup>+</sup> Vδ1 T cells drive inflammation‐induced cancer progression

Kimura, Yoshitaka; Nagai, Naomi; Tsunekawa, Naoki; Sato-Matsushita, Marimo; Yoshimoto, Takayuki; Daniel, J.; Iwakura, Yoichiro; Yagita, Hideo; Okada, Futoshi; Tahara, Hideaki; Saiki, Ikuo; Irimura, Tatsuro; Hayakawa, Yoshihiro

doi:10.1111/cas.13005

Cited by 27 publications

(18 citation statements)

References 43 publications

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“…The cytokine IL17A supports the tumor-promoting immune response and counteracts the antitumor function of IFNg (32)(33)(34). We found that NK-cell depletion did not affect the in vivo growth of MCA205-Luc2 cells in IL17A-deficient (IL17 KO) mice ( Fig.…”

Section: Il17a-neutrophil Axis Promoted Cancer Cell Growth In the Absmentioning

confidence: 73%

NK Cells Control Tumor-Promoting Function of Neutrophils in Mice

Ogura

Sato-Matsushita

Yamamoto

et al. 2018

Cancer Immunology Research

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Although natural killer (NK) cells are recognized as direct antitumor effectors, the ability of NK cells to control cancer-associated inflammation, which facilitates tumor progression, remains unknown. In this study, we demonstrate that NK cells control tumor-promoting inflammation through functional modification of neutrophils. NK cells control the tumor-promoting function of neutrophils through an IFNγ-dependent mechanism. Tumor progression in an NK cell-depleted host is diminished when the IL17A-neutrophil axis is absent. In NK cell-depleted mice, neutrophils acquire a tumor-promoting phenotype, characterized by upregulation of VEGF-A expression, which promotes tumor growth and angiogenesis. A VEGFR inhibitor which preferentially suppressed tumor growth in NK cell-depleted mice was dependent on neutrophils. Furthermore, the systemic neutropenia caused by an antimetabolite treatment showed an anticancer effect only in mice lacking NK cells. Thus, NK cells likely control the tumor-promoting and angiogenic function of neutrophils.

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Section: Il17a-neutrophil Axis Promoted Cancer Cell Growth In the Absmentioning

confidence: 73%

NK Cells Control Tumor-Promoting Function of Neutrophils in Mice

Ogura

Sato-Matsushita

Yamamoto

et al. 2018

Cancer Immunology Research

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“…Importantly, in human cancers, γδ17 T cells were also observed and associated with advanced stages of disease in colorectal and squamous cell skin tumors [ 13 , 14 ] and decreased survival of patients with gallbladder cancer [ 15 ]. Of note, the Vδ1 + subpopulation of human γδ T cells was reported to be a major source of IL-17 in colon cancer [ 13 ] and squamous cell skin cancer [ 14 ] patients and to promote inflammation-induced cancer progression [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

Tumor-associated neutrophils suppress pro-tumoral IL-17+ γδ T cells through induction of oxidative stress

et al. 2018

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Interleukin 17 (IL-17)–producing γδ T cells (γδ17 T cells) have been recently found to promote tumor growth and metastasis formation. How such γδ17 T-cell responses may be regulated in the tumor microenvironment remains, however, largely unknown. Here, we report that tumor-associated neutrophils can display an overt antitumor role by strongly suppressing γδ17 T cells. Tumor-associated neutrophils inhibited the proliferation of murine CD27− Vγ6+ γδ17 T cells via induction of oxidative stress, thereby preventing them from constituting the major source of pro-tumoral IL-17 in the tumor microenvironment. Mechanistically, we found that low expression of the antioxidant glutathione in CD27− γδ17 T cells renders them particularly susceptible to neutrophil-derived reactive oxygen species (ROS). Consistently, superoxide deficiency, or the administration of a glutathione precursor, rescued CD27− Vγ6+ γδ17 T-cell proliferation in vivo. Moreover, human Vδ1+ γδ T cells, which contain most γδ17 T cells found in cancer patients, also displayed low glutathione levels and were potently inhibited by ROS. This work thus identifies an unanticipated, immunosuppressive yet antitumoral, neutrophil/ROS/γδ17 T-cell axis in the tumor microenvironment.

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“…Vδ1 γδ T cells are another subgroup of recently discovered γδ T cells with protumor activity. Vδ1 γδ T cells are involved in inflammation-induced cancer progression, dependent on the production of IL-17A [ 73 ]. In another report, Vδ1 γδ T cells have been reported to strongly secrete TGF-β.…”

Section: γδ T Cells As Friends In Cancer Developmentmentioning

confidence: 99%

Gamma-delta (γδ) T cells: friend or foe in cancer development?

2018

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Backgroundγδ T cells are a distinct subgroup of T cells containing T cell receptors (TCRs) γ and TCR δ chains with diverse structural and functional heterogeneity. As a bridge between the innate and adaptive immune systems, γδ T cells participate in various immune responses during cancer progression. Because of their direct/indirect antitumor cytotoxicity and strong cytokine production ability, the use of γδ T cells in cancer immunotherapy has received a lot of attention over the past decade.Main textDespite the promising potential of γδ T cells, the efficacy of γδ T cell immunotherapy is limited, with an average response ratio of only 21%. In addition, research over the past 2 years has shown that γδ T cells could also promote cancer progression by inhibiting antitumor responses, and enhancing cancer angiogenesis. As a result, γδ T cells have a dual effect and can therefore be considered as being both “friends” and “foes” of cancer. In order to solve the sub-optimal efficiency problem of γδ T cell immunotherapy, we review recent observations regarding the antitumor and protumor activities of major structural and functional subsets of human γδ T cells, describing how these subsets are activated and polarized, and how these events relate to subsequent effects in cancer immunity. A mixture of both antitumor or protumor γδ T cells used in adoptive immunotherapy, coupled with the fact that γδ T cells can be polarized from antitumor cells to protumor cells appear to be the likely reasons for the mild efficacy seen with γδ T cells.ConclusionThe future holds the promise of depleting the specific protumor γδ T cell subgroup before therapy, choosing multi-immunocyte adoptive therapy, modifying the cytokine balance in the cancer microenvironment, and using a combination of γδ T cells adoptive immunotherapy with immune checkpoint inhibitors.

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IL‐17A‐producing CD30⁺ Vδ1 T cells drive inflammation‐induced cancer progression

Cited by 27 publications

References 43 publications

NK Cells Control Tumor-Promoting Function of Neutrophils in Mice

NK Cells Control Tumor-Promoting Function of Neutrophils in Mice

Tumor-associated neutrophils suppress pro-tumoral IL-17+ γδ T cells through induction of oxidative stress

Gamma-delta (γδ) T cells: friend or foe in cancer development?

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IL‐17A‐producing CD30+ Vδ1 T cells drive inflammation‐induced cancer progression

Cited by 27 publications

References 43 publications

NK Cells Control Tumor-Promoting Function of Neutrophils in Mice

NK Cells Control Tumor-Promoting Function of Neutrophils in Mice

Tumor-associated neutrophils suppress pro-tumoral IL-17+ γδ T cells through induction of oxidative stress

Gamma-delta (γδ) T cells: friend or foe in cancer development?

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IL‐17A‐producing CD30⁺ Vδ1 T cells drive inflammation‐induced cancer progression