PD1和PDL1的单药治疗已在第四期尿路上皮癌中显示了临床疗效，并已整合到当前临床实践中。然而，只有少数接受单一免疫检查点阻断治疗的患者经历了抗肿瘤反应。肿瘤免疫微环境中的初级刺激或抑制因子可能在缺乏反应方面起到了作用。CTLA4是活化T细胞上的一种抑制性检查点，在复发尿路上皮癌中作为治疗靶点与抗PD1或抗PDL1治疗联合研究。在局部晚期的尿路上皮癌中，这种联合治疗方法在术前应用显示出了鼓舞人心的抗肿瘤效果。我们认为，预先存在的肿瘤内T细胞免疫对于联合治疗的反应并非必要条件，CTLA4阻断的附加价值可能涉及扩大外周T细胞的刺激，从而将免疫冷漠性肿瘤转化为热点肿瘤。©2023. Springer Nature Limited.

Anti-PD1 and anti-PDL1 monotherapies have shown clinical efficacy in stage IV urothelial cancer and are integrated into current clinical practice. However, only a small number of the patients treated with single-agent checkpoint blockade experience an antitumour response. Insufficient priming or inhibitory factors in the tumour immune microenvironment might have a role in the lack of response. CTLA4 is an inhibitory checkpoint on activated T cells that is being studied as a therapeutic target in combination with anti-PD1 or anti-PDL1 therapies in advanced urothelial cancer. In locally advanced urothelial cancer, this combination approach has shown encouraging antitumour effects when administered pre-operatively. We believe that the presence of pre-existing intratumoural T cell immunity is not a prerequisite for response to combination therapy and that the additional value of CTLA4 blockade might involve the broadening of peripheral T cell priming, thereby transforming immunologically cold tumours into hot tumours.© 2023. Springer Nature Limited.