小鼠肿瘤模型中 T 细胞调控条件下异位 ULBP2 与 CD8(+) T 细胞 NKG2D 表达降低相关

UL16-binding protein 2 (ULBP2), a ligand for the activating receptor NKG2D, plays a dual role in tumor immunity, promoting immune activation or suppression, depending on the context. To investigate its impact on CD4 + CD25 + T cell-targeted immunotherapies, we used a syngeneic CT26 colon cancer model engineered to express ULBP2 and compared tumor growth and tumor-infiltrating lymphocyte (TIL) profiles in control and ULBP2-expressing tumors treated with anti-CD4, anti-CD25, or anti-CTLA-4 antibodies. Tumor growth was uniformly assessed on day 21 post-transplantation, and TIL analysis was performed in groups with evaluable residual tumors.

Anti-CD4 antibody significantly suppressed tumor growth in mock-transfected tumors, while no significant suppression was observed in ULBP2-expressing tumors. Anti-CD25 antibody had limited efficacy in mock tumors and tended to promote tumor growth in ULBP2-expressing tumors. Following these treatments, ULBP2 expression was associated with reduced NKG2D expression in CD8 + effector memory T cells, particularly PD-1 high subsets. In contrast, anti-CTLA-4 antibody treatment induced marked tumor regression irrespective of ULBP2 expression.

These findings suggest that ULBP2-NKG2D signaling may contribute to altered CD8 + T cell phenotypes under T cell-modulatory conditions, potentially impacting the outcome of CD4 + CD25 + T cell-targeted therapies and providing insights for optimizing immunotherapeutic strategies.