IL-21-mediated expansion of Vγ9Vδ2 T cells is limited by the Tim-3 pathway

Wu, Kan; Zhao, Haijun; Xiu, Yanghui; Li, Zhifeng; Zhao, Jiang; Xie, Shiting; Zeng, Hanyan; Zhang, Haiping; Yu, Lian; Xu, Bing

doi:10.1016/j.intimp.2019.01.027

Cited by 19 publications

(16 citation statements)

References 26 publications

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“…50 The checkpoint molecule Tim-3 limited the expansion of Vδ2 T cells following their culture with IL-21. 51 The targeting of BTN3A molecules with anti-BTN3A 20.1 monoclonal antibodies (mAbs) strongly enhanced the cytolytic functions of Vδ2 T cells against pancreatic ductal adenocarcinoma. 52 In this study, both MIH35 and B7-H3 siRNA treatment significantly enhanced, while 4H7 treatment markedly suppressed the cytotoxic effect of Vδ2 T cells on colon cancer cell lines.…”

Section: Discussionmentioning

confidence: 99%

B7-H3 inhibits the IFN-γ-dependent cytotoxicity of Vγ9Vδ2 T cells against colon cancer cells

Shi

Wang

et al. 2020

OncoImmunology

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The immunoregulatory protein B7-H3, a member of the B7 family, has been confirmed to be highly expressed in colon cancer. However, the exact influence of B7-H3 on the features and antitumor ability of γδT cells in colon cancer remains unknown. In the present study, we investigated that the proportions of B7-H3 + γδT cells were distinctly increased in the peripheral blood and tumor tissues of colon cancer patients. B7-H3 blockade or knockdown promoted proliferation, inhibited cell apoptosis and induced the expression of activation markers (CD25 and CD69) on Vδ2 T cells. In contrast, treatment with the B7-H3 agonist 4H7 had the opposite effect. Furthermore, B7-H3 suppressed IFN-γ expression by inhibiting T-bet in Vδ2 T cells. Moreover, B7-H3 mediated the inhibition of Vδ2 T cell cytotoxicity via the downregulation of IFN-γ and perforin/granzyme B expression. More importantly, blocking the B7-H3 function significantly enhanced the cytotoxicity of Vδ2 T cells against colon cancer cells in vivo. Therefore, the inhibition or blockade of B7-H3 is a potential immunotherapeutic approach for colon cancer.

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Section: Discussionmentioning

confidence: 99%

B7-H3 inhibits the IFN-γ-dependent cytotoxicity of Vγ9Vδ2 T cells against colon cancer cells

Shi

Wang

et al. 2020

OncoImmunology

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“…These cells also express significantly higher TIM-3 levels than healthy Vγ9Vδ2 T cells and upregulate TIM-3 after IL-21 stimulation. Blocking TIM-3 increases the proliferation and reactivity of Vγ9Vδ2 T cells to IL-21 stimulation (144). These data indicate the existence of druggable interconnections between ICP/ICP-L and FA metabolism mediated by cytokines like IL-21.…”

Section: Combination With Modulators Of Fatty Acid Metabolismmentioning

confidence: 69%

Metabolic approaches to rescue antitumor V gamma 9V delta 2 T-cell functions in myeloma

Massaia¹

2020

Front Biosci

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Introduction 3. Interplay between metabolic checkpoints (MCP) and ICP/ICP-L 4. Metabolic alterations in the MM TME 5. Mevalonate (Mev) pathway: another MCP in MM TME 6. Metabolic alterations which can impair Vγ9Vδ2 T-cell functions and influence ICP/ICP-L expression 7. Perspectives: Targeting TME immunometabolism to improve ICP/ICP -L blockade and antitumor Vγ9Vδ2 T-cell functions in MM 7.1. Combination with drugs targeting glycolytic and intermediate metabolism 7.2. Targeting the TCA cycle and mitochondrial metabolism 7.3. Combination with hypoxia inhibitors 7.4. Combination with Mev pathway inhibitors 7.5. Combination with modulators of fatty acid metabolism 7.6. Combination with IDO inhibitors 7.7. Combination with Arg1 inhibitors 7.8. Targeting glutamine uptake and glutamine metabolism 7.9. Combination with ADO pathway inhibitors 8. Concluding remarks 9. Acknowledgment 10. References

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“…γδT cells are highly efficient in promoting B cell maturation and producing IgM, IgG, and IgA antibodies. Vδ2Vγ9 T cells express IL-21R on their surface, which is enhanced upon HMB-PP induced irritation ( 111 , 112 ). Activated Vδ2Vγ9T cells express CXCL13, CXCR5, and ICOS and upregulate the expression of B cell surface markers CD25, CD69, CD40, and CD86.…”

Section: Biological Effects Of γδT Cellsmentioning

confidence: 99%

Gamma Delta T Cells and Their Pathogenic Role in Psoriasis

Qian

Wang

et al. 2021

Front. Immunol.

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γδT cells are an unconventional population of T lymphocytes that play an indispensable role in host defense, immune surveillance, and homeostasis of the immune system. They display unique developmental, distributional, and functional patterns and rapidly respond to various insults and contribute to diverse diseases. Although γδT cells make up only a small portion of the total T cell pool, emerging evidence suggest that aberrantly activated γδT cells may play a role in the pathogenesis of psoriasis. Dermal γδT cells are the major IL-17-producing cells in the skin that respond to IL-23 stimulation. Furthermore, γδT cells exhibit memory-cell-like characteristics that mediate repeated episodes of psoriatic inflammation. This review discusses the differentiation, development, distribution, and biological function of γδT cells and the mechanisms by which they contribute to psoriasis. Potential therapeutic approaches targeting these cells in psoriasis have also been detailed.

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IL-21-mediated expansion of Vγ9Vδ2 T cells is limited by the Tim-3 pathway

Cited by 19 publications

References 26 publications

B7-H3 inhibits the IFN-γ-dependent cytotoxicity of Vγ9Vδ2 T cells against colon cancer cells

B7-H3 inhibits the IFN-γ-dependent cytotoxicity of Vγ9Vδ2 T cells against colon cancer cells

Metabolic approaches to rescue antitumor V gamma 9V delta 2 T-cell functions in myeloma

Gamma Delta T Cells and Their Pathogenic Role in Psoriasis

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