Immunogenic cell death (ICD) improves the T cell response against different tumors, indicating that ICD can enhance the antitumor immunity elicited by the anti-checkpoint antibody anti-programmed death 1 (anti-PD-1). In the present study, we reported a synergistic and durable immune-mediated antitumor response elicited by the combined treatment of SR-4835, a CDK12/13 specific inhibitor, with PD-1 blockade in a syngeneic mouse model. The developed combination therapy elicited antitumor activity in immunocompetent mouse tumor models. Furthermore, the SR-4835-treated tumor cells exhibited characteristics of ICD, including the release of high mobility group box 1 (HMGB1) and ATP and calreticulin (CRT) translocation. This activity led to a significant T-cell-dependent tumor suppression. The enhanced dendritic cell (DC) and infiltration of T cells activation in the tumors treated with both SR-4835 and anti-PD-1 indicate that this combination treatment promotes an improved immune response. Therefore, the results of the present study demonstrate the potential of CDK12/13 inhibition combined with checkpoint inhibition in breast cancer treatment.

免疫原性细胞死亡（ICD）改善了对于不同肿瘤的T细胞应答，这表明ICD可以增强由抗关卡抗体抗程序性死亡1引起的抗肿瘤免疫（抗-PD-1）。在本研究中，我们报道了在同系小鼠模型中，将CD-4 / 12特异性抑制剂SR-4835与PD-1阻断剂联合治疗可产生协同和持久的免疫介导的抗肿瘤反应。开发的联合疗法在具有免疫能力的小鼠肿瘤模型中引发了抗肿瘤活性。此外，经SR-4835处理的肿瘤细胞表现出ICD的特征，包括释放高迁移率族盒1（HMGB1）和ATP和钙网蛋白（CRT）易位。这种活性导致了显着的T细胞依赖性肿瘤抑制作用。用SR-4835和抗抑郁药治疗的肿瘤中增强的树突状细胞（DC）和T细胞活化的浸润-PD-1表明该联合治疗促进了改善的免疫反应。因此，本研究的结果证明了CDK12 / 13抑制与检查点抑制相结合在乳腺癌治疗中的潜力。