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Published in: Cancer Immunology, Immunotherapy 6/2023

Open Access 21-01-2023 | osteosarcoma | Research

Human γδ T cells induce CD8+ T cell antitumor responses via antigen-presenting effect through HSP90-MyD88-mediated activation of JNK

Authors: Shengdong Wang, Hengyuan Li, Tao Chen, Hao Zhou, Wenkan Zhang, Nong Lin, Xiaohua Yu, Yu Lou, Binghao Li, Eloy Yinwang, Zenan Wang, Keyi Wang, Yucheng Xue, Hao Qu, Peng Lin, Hangxiang Sun, Wangsiyuan Teng, Haochen Mou, Xupeng Chai, Zhijian Cai, Zhaoming Ye

Published in: Cancer Immunology, Immunotherapy | Issue 6/2023

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Abstract

Human Vγ9Vδ2 T cells have attracted considerable attention as novel alternative antigen-presenting cells (APCs) with the potential to replace dendritic cells in antitumor immunotherapy owing to their high proliferative capacity and low cost. However, the utility of γδ T cells as APCs to induce CD8+ T cell-mediated antitumor immune response, as well as the mechanism by which they perform APC functions, remains unexplored. In this study, we found that activated Vγ9Vδ2 T cells were capable of inducing robust CD8+ T cell responses in osteosarcoma cells. Activated γδ T cells also effectively suppressed osteosarcoma growth by priming CD8+ T cells in xenograft animal models. Mechanistically, we further revealed that activated γδ T cells exhibited increased HSP90 production, which fed back to upregulate MyD88, followed by JNK activation and a subsequent improvement in CCL5 secretion, leading to enhanced CD8+ T cell cross-priming. Thus, our study suggests that Vγ9Vδ2 T cells represent a promising alternative APC for the development of γδ T cell-based tumor immunotherapy.
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Metadata
Title
Human γδ T cells induce CD8+ T cell antitumor responses via antigen-presenting effect through HSP90-MyD88-mediated activation of JNK
Authors
Shengdong Wang
Hengyuan Li
Tao Chen
Hao Zhou
Wenkan Zhang
Nong Lin
Xiaohua Yu
Yu Lou
Binghao Li
Eloy Yinwang
Zenan Wang
Keyi Wang
Yucheng Xue
Hao Qu
Peng Lin
Hangxiang Sun
Wangsiyuan Teng
Haochen Mou
Xupeng Chai
Zhijian Cai
Zhaoming Ye
Publication date
21-01-2023
Publisher
Springer Berlin Heidelberg
Published in
Cancer Immunology, Immunotherapy / Issue 6/2023
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI
https://doi.org/10.1007/s00262-023-03375-w

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