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

被引：6

作者：

Wang, Shengdong ^{[1
,2
,3
]}

Li, Hengyuan ^{[1
,2
,3
]}

Chen, Tao ^{[1
,2
,3
]}

Zhou, Hao ^{[1
,2
,3
]}

Zhang, Wenkan ^{[1
,2
,3
]}

Lin, Nong ^{[1
,2
,3
]}

Yu, Xiaohua ^{[1
,2
,3
]}

Lou, Yu ^{[4
]}

Li, Binghao ^{[1
,2
,3
]}

Yinwang, Eloy ^{[1
,2
,3
]}

Wang, Zenan ^{[1
,2
,3
]}

Wang, Keyi ^{[1
,2
,3
]}

Xue, Yucheng ^{[1
,2
,3
]}

Qu, Hao ^{[1
,2
,3
]}

Lin, Peng ^{[1
,2
,3
]}

Sun, Hangxiang ^{[1
,2
,3
]}

Teng, Wangsiyuan ^{[1
,2
,3
]}

Mou, Haochen ^{[1
,2
,3
]}

Chai, Xupeng ^{[1
,2
,3
]}

Cai, Zhijian ^{[5
]}

Ye, Zhaoming ^{[1
,2
,3
]}

机构：

[1] Second Affiliated Hosp Zhejiang Univ Sch Med, Musculoskeletal Tumor Ctr, Dept Orthoped, Hangzhou 310009, Peoples R China

[2] Zhejiang Univ, Inst Orthoped Res, Hangzhou 310009, Peoples R China

[3] Key Lab Motor Syst Dis Res & Precis Therapy Zhejia, Hangzhou, Zhejiang, Peoples R China

[4] Zhejiang Univ Sch Med, Affiliated Hosp 1, Dept Hepatobiliary & Pancreat Surg, Hangzhou, Peoples R China

[5] Zhejiang Univ Sch Med, Affiliated Hosp 2, Inst Immunol, Dept Orthopaed, Hangzhou 310009, Peoples R China

来源：

CANCER IMMUNOLOGY IMMUNOTHERAPY | 2023年 / 72卷 / 06期

基金：

中国国家自然科学基金;

关键词：

gamma delta T cells; Antigen presentation; Tumor immunotherapy; Osteosarcoma; CROSS-PRESENTATION; TUMOR-ANTIGEN; LINES; IMMUNOTHERAPY; MECHANISM; VACCINES; CD4(+);

D O I：

10.1007/s00262-023-03375-w

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Human V gamma 9V delta 2 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 gamma delta 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 V gamma 9V delta 2 T cells were capable of inducing robust CD8(+) T cell responses in osteosarcoma cells. Activated gamma delta T cells also effectively suppressed osteosarcoma growth by priming CD8(+) T cells in xenograft animal models. Mechanistically, we further revealed that activated gamma delta 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 V gamma 9V delta 2 T cells represent a promising alternative APC for the development of gamma delta T cell-based tumor immunotherapy.

引用

页码：1803 / 1821

页数：19

共 51 条

[31] EBV-transformed lymphoblastoid cell lines as vaccines against cancer testis antigen-positive tumors [J].