肿瘤细胞治疗研究
英文原题：Recent advances in immunotherapy for bladder cancer: mechanisms, clinical applications, and future perspectives.
我们最后概述未来的研究方向，重点在于克服治疗耐药性、完善预测和预后生物标志物，以及开发下一代免疫疗法以改善患者的临床结局。
过去十年见证了膀胱癌治疗的范式转变，这一转变由免疫治疗的重大进展所推动。靶向 PD-1/PD-L1 和 CTLA-4 的免疫检查点抑制剂（ICIs）、包括CAR-T 细胞疗法在内的过继性细胞治疗、溶瘤病毒以及新型免疫调节剂，已经改变了非肌层浸润性膀胱癌（NMIBC）和晚期尿路上皮癌（UC）的治疗格局。本综述全面分析了膀胱癌免疫治疗的最新进展，重点关注其潜在的分子和细胞机制、关键临床试验证据以及新出现的耐药途径。我们重点阐述了 ICIs 迅速扩展的治疗作用，以及针对肿瘤相关抗原（包括 NECTIN4、PSMA 和 FR）的 CAR-T 细胞疗法等创新模式。本文全面综述了新出现的免疫治疗靶点和治疗模式。我们批判性评估了关键临床试验，并系统评价了联合策略——包括 ICIs 联合化疗、放疗、靶向治疗或抗体药物偶联物（ADCs）。本文探讨了肿瘤微环境（TME）的关键决定因素——如免疫抑制性细胞群、调节性细胞因子和代谢屏障——在介导治疗耐药中的作用。本文总结了预测治疗反应的生物标志物——包括 PD-L1 表达和肿瘤突变负荷——并整合了最新的临床和转化研究证据。我们最后概述未来的研究方向，重点在于克服治疗耐药性、完善预测和预后生物标志物，以及开发下一代免疫疗法以改善患者的临床结局。
The past decade has witnessed a paradigm shift in the treatment of bladder cancer, propelled by significant advances in immunotherapy. Immune checkpoint inhibitors (ICIs) targeting PD-1/PD-L1 and CTLA-4, adoptive cellular therapies including chimeric antigen receptor T-cell (CAR-T) therapy, oncolytic viruses, and novel immunomodulatory agents have transformed the therapeutic landscape for both non-muscle-invasive bladder cancer (NMIBC) and advanced urothelial carcinoma (UC). This review provides a comprehensive analysis of recent advances in bladder cancer immunotherapy, with a focus on underlying molecular and cellular mechanisms, key clinical trial evidence, and emerging resistance pathways. We highlight the rapidly expanding therapeutic roles of ICIs, alongside innovative modalities such as CAR-T cell therapy directed against tumor-associated antigens-including NECTIN4, PSMA, and FR . Emerging immunotherapeutic targets and therapeutic modalities are comprehensively reviewed. We critically evaluate key clinical trials and systematically assess combination strategies-including ICIs combined with chemotherapy, radiotherapy, targeted therapy, or antibody-drug conjugates (ADCs). Key determinants of the tumor microenvironment (TME)-such as immunosuppressive cell populations, regulatory cytokines, and metabolic barriers-are examined in the context of their roles in mediating therapeutic resistance. Biomarkers predictive of treatment response-including PD-L1 expression and tumor mutational burden-are summarized, integrating recent clinical and translational evidence. We conclude by outlining future research directions focused on overcoming therapeutic resistance, refining predictive and prognostic biomarkers, and developing next-generation immunotherapies to improve clinical outcomes for patients.
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