Lisovska Natalya
Chemotherapy Department, Center of Oncology, 'Cyber Clinic of Spizhenko', Kapitanovka, Kyiv 08112, Ukraine.
Oncol Lett. 2022 Jun;23(6):190. doi: 10.3892/ol.2022.13310. Epub 2022 Apr 29.
Immunotherapy with checkpoint inhibitors (antibodies that target and block immune checkpoints in the tumor microenvironment) is included in the standard of care for patients with different types of malignancy, such as melanoma, renal cell and urothelial carcinoma, lung cancer etc. The introduction of this new immunotherapy has altered the view on potential targets for treatment of solid tumors from tumor cells themselves to their immune microenvironment; this has led to a reconsideration of the mechanisms of tumor-associated immunity. However, only a subset of patients benefit from immunotherapy and patient response is often unpredictable, even with known initial levels of prognostic markers; the biomarkers for favorable response are still being investigated. Mechanisms of immune checkpoint inhibitors efficiency, as well as the origins of treatment failure, require further investigation. From a clinical standpoint, discrepancies between the theoretical explanation of inhibitors of immune checkpoint actions at the cellular level and their deployment at a tissue/organ level impede the effective clinical implementation of novel immune therapy. The present review assessed existing experimental and clinical data on functional activity of inhibitors of immune checkpoints to provide a more comprehensive picture of their mechanisms of action on a cellular and higher levels of biological organization.
使用检查点抑制剂（靶向并阻断肿瘤微环境中免疫检查点的抗体）进行免疫治疗已被纳入不同类型恶性肿瘤患者的标准治疗方案，如黑色素瘤、肾细胞癌和尿路上皮癌、肺癌等。这种新免疫疗法的引入改变了对实体瘤治疗潜在靶点的看法，从肿瘤细胞本身转向其免疫微环境；这引发了对肿瘤相关免疫机制的重新思考。然而，只有一部分患者能从免疫治疗中获益，而且即使已知初始预后标志物水平，患者的反应往往也不可预测；仍在研究预测良好反应的生物标志物。免疫检查点抑制剂的作用机制以及治疗失败的原因仍需进一步研究。从临床角度来看，免疫检查点抑制剂在细胞水平的作用理论解释与其在组织/器官水平的应用之间存在差异，这阻碍了新型免疫疗法的有效临床应用。本综述评估了关于免疫检查点抑制剂功能活性的现有实验和临床数据，以便更全面地了解其在细胞及更高生物组织水平上的作用机制。
