CELL INTELLIGENCE · 肿瘤细胞治疗研究

BACKGROUND: Adoptive cell transfer (ACT) therapy shows great promise in ovarian cancer. In addition to the classic αβ T cells, γδ T cells have become a very important anti-tumor weapon in tumor immunotherapy, especially in hematological tumors, due to their high in vitro expansion efficiency and high tumor killing activity. However, in solid tumors, especially cold tumors such as ovarian cancer, the anti-tumor effect of γδ T cells and the key factors affecting and regulating the anti-tumor ability of γδ T cells are still unclear. METHOD: The functional characteristics of Vγ9Vδ2 T cells in ovarian cancer, along with the molecules and pathways mediating their interaction with tumor cells, were preliminarily explored. This was done using databases such as The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), in addition to RNA sequencing (RNA-seq). Furthermore, Vγ9Vδ2 T cells were co-cultured with ovarian cancer tumor cell lines to validate the molecules and pathways affecting Vγ9Vδ2 T cell function through flow cytometry. RESULTS: Vγ9Vδ2 T cells in ovarian cancer have strong anti-tumor properties. High expression of BTN3A1 in tumor cells reduces the activation of expanded Vγ9Vδ2 T cells, increases expression of exhaustion related molecules, and raises apoptosis levels in these cells. Blocking the T cell receptor (TCR) can eliminate the effect of BTN3A1 on exhaustion of Vγ9Vδ2 T cells. CONCLUSION: BTN3A1 activates Vγ9Vδ2 T cells but also induces their exhaustion through the TCR signaling pathway. BTN3A1 may serve as a regulator of activation-induced exhaustion in γδ T cells. Targeting downstream related molecules of BTN3A1 is of great significance for enhancing adoptive Vγ9Vδ2 T cells transfer therapy.