Non-muscle invasive bladder cancer (NMIBC) represents a significant clinical challenge due to its high recurrence rate and need for frequent monitoring. The current treatment modality is bacillus Calmette–Guérin (BCG) therapy combined with chemotherapy after transurethral resection of the bladder tumor (TURBT), which is highly effective in most patients. Yet, the cancer becomes resistant to these treatments in 30–40% of patients, necessitating the need for new treatment modalities. In the cancer world, the development of immune checkpoint inhibitors that target molecules, such as programmed cell death protein-1 (PD-1), its ligand, PD-L1, and Cytotoxic T-lymphocyte-associated protein-4 (CTLA-4), have revolutionized the treatment of many cancer types. PD-1/PD-L1 and CTLA-4 are shown to be upregulated in NMIBC in certain circumstances. PD-1/PD-L1 interactions play a role in immune evasion by suppressing T cell activity within the tumor microenvironment (TME), while the binding of CTLA-4 on T cells leads to downregulation of the immune response, making these pathways potential immunotherapeutic targets in NMIBC. This review seeks to understand the role of these therapies in treating NMIBC. We explore the cellular and non-cellular immune landscape in the TME of NMIBC, including Tregs, T effector cells, macrophages, B cells, and relevant cytokines. We also discuss the biological role of PD-1/PD-L1 and CTLA-4 while covering the rationale for these immunotherapies in NMIBC. Finally, we cover key clinical trials that have studied these treatments in NMIBC clinically. Such a study will be helpful for urologists and oncologists to manage patients with NMIBC more effectively.
非肌层浸润性膀胱癌（NMIBC）因其高复发率和需要频繁监测而构成重大临床挑战。目前的标准治疗方案为经尿道膀胱肿瘤切除术（TURBT）后联合卡介苗（BCG）与化疗，该方案对多数患者疗效显著。然而，约30%-40%的患者会对这些治疗产生耐药性，因此亟需开发新的治疗策略。在肿瘤治疗领域，针对程序性细胞死亡蛋白-1（PD-1）、其配体PD-L1以及细胞毒性T淋巴细胞相关蛋白-4（CTLA-4）等分子的免疫检查点抑制剂的发展，已彻底改变了多种癌症的治疗格局。研究表明，在特定情况下NMIBC中PD-1/PD-L1和CTLA-4表达会上调。PD-1/PD-L1的相互作用通过抑制肿瘤微环境（TME）中的T细胞活性参与免疫逃逸，而T细胞上CTLA-4的结合会导致免疫应答下调，这些机制使得相关通路成为NMIBC潜在的免疫治疗靶点。本综述旨在探讨此类疗法在NMIBC治疗中的作用。我们系统分析了NMIBC肿瘤微环境中的细胞与非细胞免疫景观，包括调节性T细胞、效应T细胞、巨噬细胞、B细胞及相关细胞因子。同时阐述了PD-1/PD-L1和CTLA-4的生物学功能，并论证了这些免疫疗法应用于NMIBC的理论依据。最后，汇总了针对NMIBC开展的相关关键临床试验。本研究将为泌尿外科医师和肿瘤学家更有效地管理NMIBC患者提供重要参考。
肿瘤(癌症)患者之家