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Human γδ T cells induce CD8+ T cell antitumor responses via antigen-presenting effect through HSP90-MyD88-mediated activation of JNK.
- Source :
- Cancer Immunology, Immunotherapy; Jun2023, Vol. 72 Issue 6, p1803-1821, 19p
- Publication Year :
- 2023
-
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<superscript>+</superscript> 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<superscript>+</superscript> T cell responses in osteosarcoma cells. Activated γδ T cells also effectively suppressed osteosarcoma growth by priming CD8<superscript>+</superscript> 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<superscript>+</superscript> 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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 03407004
- Volume :
- 72
- Issue :
- 6
- Database :
- Complementary Index
- Journal :
- Cancer Immunology, Immunotherapy
- Publication Type :
- Academic Journal
- Accession number :
- 163829476
- Full Text :
- https://doi.org/10.1007/s00262-023-03375-w