TIGIT 阻断在三阴性乳腺癌模型中增强 PD-1 阻断联合放疗的疗效

We analyzed public transcriptomic data to identify the expression patterns of TIGIT on T cells in breast cancer and its prognostic impact. In addition, a murine TNBC model was utilized to evaluate the effects of αPD-1, local RT, and αTIGIT. T cells in tumors, tumor-draining lymph nodes (TdLNs), and the spleen were analyzed to assess the antitumor immune responses upon the treatments.

The analysis revealed that TIGIT is predominantly expressed on T cells within breast cancer, and the expression of TIGIT was associated with poor outcomes in TNBC patients. In the murine model, the combination of αPD-1 and RT increased TIGIT + CD226 + CD8 + TILs, which are crucial for the efficacy of αTIGIT. Adding αTIGIT to αPD-1 and RT (αPD-1/RT) resulted in a synergistic antitumor effect, which was accompanied by increased infiltration of CD8 + TILs in both irradiated and nonirradiated tumors by the triple combination therapy compared to αPD-1/RT. The triple combination therapy also resulted in a less exhausted phenotype among CD8 + TILs and increased the proliferation of splenic CD8 + T cells. Moreover, αTIGIT significantly reduced Tregs in tumors, TdLNs, and the spleen when combined with αPD-1/RT.

αTIGIT exhibits synergistic effects when added to αPD-1/RT by increasing the infiltration and activation of CD8 + TILs while reducing Tregs. The study suggests that αTIGIT could be an effective strategy to enhance the antitumor efficacy of αPD-1 and RT in TNBC.