Department of Pathology, Division of Anatomic Pathology, University of Virginia, Charlottesville, VA, USA.
Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, University of Virginia, Charlottesville, VA, USA.
Mod Pathol. 2022 Feb;35(2):142-151. doi: 10.1038/s41379-021-00882-y. Epub 2021 Sep 7.
Checkpoint inhibitor-based immunotherapy is increasingly used in the treatment of gynecologic cancers, and most often targets the PD-1/PD-L1 axis. Pathologists should be familiar with the biomarkers required to determine candidacy for these treatments based on existing FDA approvals, including mismatch repair protein immunohistochemistry, microsatellite instability testing, tumor mutation burden testing, and PD-L1 immunohistochemistry. This review summarizes the rationale behind these treatments and their associated biomarkers and delivers guidance on how to utilize and readout these tests. It also introduces additional biomarkers which may provide information regarding immunotherapeutic vulnerability in the future such as neoantigen load; POLE mutation status; and immunohistochemical expression of immunosuppressive checkpoints like LAG-3, TIM-3, TIGIT, and VISTA; immune-activating checkpoints such as CD27, CD40, CD134, and CD137; enzymes such as IDO-1 and adenosine-related compounds; and MHC class I.
基于检查点抑制剂的免疫疗法越来越多地用于妇科癌症的治疗，并且通常针对 PD-1/PD-L1 轴。病理学家应该熟悉基于现有 FDA 批准的这些治疗方法所需的生物标志物，包括错配修复蛋白免疫组化、微卫星不稳定性检测、肿瘤突变负荷检测和 PD-L1 免疫组化。这篇综述总结了这些治疗方法背后的原理及其相关生物标志物，并就如何使用和解读这些检测方法提供了指导。它还介绍了其他一些生物标志物，这些生物标志物可能在未来提供有关免疫治疗脆弱性的信息，例如新抗原负荷；POLE 突变状态；以及免疫抑制检查点如 LAG-3、TIM-3、TIGIT 和 VISTA 的免疫组化表达；免疫激活检查点如 CD27、CD40、CD134 和 CD137；酶如 IDO-1 和腺苷相关化合物；以及 MHC Ⅰ类。
Zotero 插件