肿瘤组织免疫微环境塑造的新机制与临床意义  

New mechanisms and clinical significance of the modulation of tumor immune environments

作　　者：吴艳 邝栋明[1] 郑利民[1] WU Yan;KUANG DongMing;ZHENG LiMin(School of Life Sciences,Sun Yat-sen University,Guangzhou 510275,China)

机构地区：[1]中山大学生命科学学院,广州510275

出　　处：《中国科学：生命科学》2024年第9期1595-1602,共8页Scientia Sinica(Vitae)

摘　　要：免疫细胞是肿瘤微环境的重要组成成分,既能清除肿瘤,又可以被肿瘤“利用”来帮助其进展并影响治疗应答,是肿瘤防治的重要靶标.尽管近年来免疫治疗,如CAR-T和免疫检查点阻断等在多种类型肿瘤的治疗中取得突破性进展,其整体治疗的响应率仍十分有限.其中一个重要的原因在于,目前的免疫治疗策略主要靶向适应性免疫的T淋巴细胞,实际上组织中的髓系细胞(包括巨噬细胞和中性粒细胞)以及B淋巴细胞,均在T细胞抗肿瘤免疫功能的启动、维持以及耗竭等过程中发挥关键调控作用.深入理解这些细胞在肿瘤进展过程中的塑造与功能作用机制,不仅有助于更好地解析肿瘤的发生发展机制,更有望挖掘出全新的独立/联合免疫治疗靶点.二十余年来,本课题组以肝癌为主要模型,围绕肿瘤浸润髓系免疫细胞和B淋巴细胞,结合临床样本和实验模型开展系统研究,获得一系列原创性成果.结合本课题组研究成果,对肿瘤组织免疫微环境研究进行综述,并对未来研究方向及研究重点进行探讨.Immune cells are major components of the tumor microenvironment.They can eliminate cancer cells and can be“co-opted”by tumors to facilitate disease progression and impact therapeutic responsiveness.Therefore,immune cells are important targets for tumor therapy.Immune therapies,such as chimeric antigen receptor T cells and immune checkpoint blockade treatments,have gained ground-breaking progress in recent years.However,tumor responsiveness to such strategies is still limited.One of the major reasons is that most of the current immune therapies mainly target T lymphocytes of adaptive immunity,whereas many tissue-infiltrating myeloid cells(including macrophages and neutrophils)and B lymphocytes play essential roles in the initiation,maintenance,and exhaustion of T lymphocytes.Exploring the regulation and functions of tumor-associated myeloid cells and B lymphocytes would not only yield better insights into the mechanisms of tumor development but also provide novel targets for independent or combinational tumor therapies.For the past 20 years,we have focused on hepatocellular carcinoma-infiltrating myeloid cells and B lymphocytes and obtained results through a combination of clinical analysis and experimental studies.This review briefly introduces some of these results and proposes future directions for studies in the field of tumor immune environment.

关 键 词：肿瘤微环境 髓系细胞 B淋巴细胞 免疫治疗 

分 类 号：R730.3[医药卫生—肿瘤]