恶性胸膜间皮瘤免疫微环境及免疫治疗的研究进展

Advances in tumor immune microenvironment and immunotherapy of malignant pleural mesothelioma

恶性胸膜间皮瘤(malignant pleural mesothelioma,MPM)是胸膜间皮细胞癌变引起的罕见恶性肿瘤,>80%的MPM与吸入石棉纤维(asbestos fiber)所致的慢性炎症反应有关。MPM恶性程度高,生存预后差,而培美曲塞联合顺铂的标准化疗方案能使晚期MPM患者中位总生存期(overall survival,OS)延长至12个月左右。MPM的肿瘤微环境(tumor microenvironment,TME)涉及大量免疫相关细胞,对该疾病的发病和预后至关重要。TME与肿瘤治疗密切关联,以微环境为治疗靶点的抗肿瘤免疫治疗是近年肿瘤治疗的研究热点,免疫检查点抑制剂(immune checkpoint inhibitors,ICIs)的应用使肿瘤免疫治疗进入了新纪元。无论是免疫单药治疗还是联合治疗都在晚期MPM一线及二线标准治疗方面取得了显著的成果。现就恶性胸膜间皮瘤TME中主要的免疫细胞及其功能、MPM的免疫治疗及未来免疫治疗的研究方向作一概述。

Malignant pleural mesothelioma(MPM)is a rare tumor caused by malignant transformation of pleural mesothelial cells.Up to 80%of the MPM cases are associated with asbestos fiber caused chronic inflammatory responses.MPM is a highly aggressive malignancy with poor prognosis.Platinum-based chemotherapy in combination with pemetrexed has been the standard of care for advanced MPM patients,which prolonged the median overall survival to approximately 12 months.The tumor microenvironment(TME)of MPM involves a variety of immune cells which play significant roles in carcinogenesis and prognosis.TME is closely linked to treatment efficacy.Recently,anti-tumor immunotherapy targeting TME has become the hotspots in researches.Immune checkpoint inhibitors(ICIs)have revolutionized the treatment of cancer.In advanced MPM,treatment with single or dual ICIs results in robust improvements in overall survival over previous standard-of-care therapies,both in the first-line and relapsed disease settings.Here,we comprehensively summarize the major immune cells in TME of MPM,current immunotherapies and future research directions for mesothelioma.