Department of Hematopathology, Tata Memorial Hospital, Mumbai, India.
Department of Medical Oncology, Advanced Medical Research Institute, Bhubaneswar, India.
Semin Oncol. 2020 Dec;47(6):367-379. doi: 10.1053/j.seminoncol.2020.09.002. Epub 2020 Oct 24.
Advances in molecular immunology have unveiled some of the complexity of the mechanisms regulating cellular immune responses and led to the successful targeting of immune checkpoints in attempts to enhance antitumor T cell responses. Surgery, chemotherapy, and radiation therapy have been the mainstay of treatment in urologic malignancies. Immune checkpoint molecules such as cytotoxic T-lymphocyte associated protein-4, programmed cell death protein-1, and programmed death-ligand 1 have been shown to play central roles in evading cancer immunity. Thus these molecules have been targeted by inhibitors for the management of cancers forming the basis of immunotherapy. Immunotherapy is now among the first line therapeutic options for metastatic renal cell carcinomas. In advanced bladder cancer, immunotherapy is the standard of care in the second line and the first line for cisplatin ineligible patients. There continues to be ongoing research to identify the role if any of immunotherapy in testicular, prostatic, and penile cancers. The ideal biomarker for response to immunotherapy is still elusive. Although programmed death-ligand 1 immunohistochemical testing has been widely used across the globe as a biomarker for immunotherapy, companion diagnostic tests have inherent issues with testing and reporting and cannot have universal applicability. Additional biomarkers including, tumor mutational burden, deficient mismatch repair, high microsatellite instability, and immune gene expression profiling are being evaluated in various clinical trials. This review appraises the data of immunotherapy in the management of urologic malignancies.
分子免疫学的进展揭示了调节细胞免疫反应的机制的一些复杂性，并导致成功靶向免疫检查点，以试图增强抗肿瘤 T 细胞反应。手术、化疗和放疗一直是泌尿系统恶性肿瘤治疗的主要手段。细胞毒性 T 淋巴细胞相关蛋白 4、程序性细胞死亡蛋白 1 和程序性死亡配体 1 等免疫检查点分子已被证明在逃避癌症免疫方面发挥着核心作用。因此，这些分子已被抑制剂靶向，用于癌症的管理，构成免疫治疗的基础。免疫治疗现在是转移性肾细胞癌的一线治疗选择之一。在晚期膀胱癌中，免疫治疗是二线治疗的标准，也是不耐受顺铂患者的一线治疗。目前仍在进行研究，以确定免疫治疗在睾丸癌、前列腺癌和阴茎癌中的作用。对免疫治疗反应的理想生物标志物仍然难以捉摸。尽管程序性死亡配体 1 免疫组化检测已在全球范围内广泛用作免疫治疗的生物标志物，但伴随诊断检测在检测和报告方面存在固有问题，并且不能具有普遍适用性。其他生物标志物，包括肿瘤突变负担、错配修复缺陷、高微卫星不稳定性和免疫基因表达谱分析，正在各种临床试验中进行评估。本文评价了免疫治疗在泌尿系统恶性肿瘤治疗中的应用数据。
