肌层浸润性膀胱癌（BC）的默认治疗是新辅助顺铂为基础的化疗，并随后进行全膀胱切除术。然而，近年来免疫检查点抑制剂（ICI）针对PD-1/PD-L1和CTLA-4的鼓舞人心的结果导致了BC的治疗格局的迅速变化。此外，越来越清楚的是，ICI的效果高度依赖于肿瘤细胞与肿瘤免疫微环境（TIME）之间的相互作用。不同的免疫细胞参与BC的抗肿瘤反应。细胞毒性CD8+ T细胞是主要的效应细胞，还有其他免疫细胞如其他T细胞、B细胞和促炎症巨噬细胞的帮助。作为持续进行的抗肿瘤免疫反应的一部分，淋巴细胞聚集成被称为第三淋巴结结构（TLS）的簇团。肿瘤突变负荷（TMB）和免疫细胞浸润肿瘤都是建立抗肿瘤免疫反应的重要因素。相反，癌相关成纤维细胞（CAFs）中的转化生长因子β（TGF-β）信号阻止淋巴细胞的浸润，可能具有免疫抑制作用。总之，ICI的效果似乎依赖于肿瘤内在和与时间相关的参数的组合。还需要进一步研究以完全理解潜在的生物学机制，以进一步改善患者护理。原文版权©2023 van Dorp和van der Heijden。

Treatment with neoadjuvant cisplatin-based chemotherapy followed by radical cystectomy is the default treatment for muscle-invasive bladder cancer (BC). However, with the encouraging results of immune checkpoint inhibitiors (ICI) directed against PD-1/PD-L1 and CTLA-4 in recent years, the treatment landscape of BC is rapidly changing. In addition, it is becoming clear that the effect of ICI is highly dependent on the interaction between tumor cells and the tumor immune micro-environment (TIME). Different immune cells are involved in an anti-tumor response in BC. Cytotoxic CD8+ T-cells are the main effector cells, aided by other immune cells including other T-cells, B-cells and pro-inflammatory macrophages. As part of the ongoing anti-tumor immune response, lymphocytes aggregate in clusters called tertiary lymphoid structures (TLS). Tumor mutational burden (TMB) and infiltration of immune cells into the tumor are both important factors for establishing an anti-tumor immune response. In contrast, transforming growth factor beta (TGF-β) signaling in cancer-associated fibroblasts (CAFs) prevents infiltration of lymphocytes and potentially has an immunosuppressive effect. In conclusion, the effect of ICI seems to be reliant on a combination of tumor-intrinsic and TIME-related parameters. More research is needed to fully understand the underlying biological mechanisms to further improve patient care.Copyright © 2023 van Dorp and van der Heijden.