肿瘤细胞原位重编程为抗原呈递细胞的策略  

Strategies for in situ reprogramming of tumor cells into antigen-presenting cells

作　　者：林永芳 吴黎川 揭晓亮 周光飚 LIN Yongfang;WU Lichuan;JIE Xiaoliang;ZHOU Guangbiao(National Cancer Center/State Key Laboratory of Molecular Oncology,Cancer Hospital,Chinese Academy of Medical Sciences,Beijing 100021,China;Guangxi Key Laboratory of Special Biomedicine,School of Medicine,Guangxi University,Nanning 530004,China)

机构地区：[1]国家癌症中心/中国医学科学院肿瘤医院分子肿瘤学国家重点实验室,北京100021 [2]广西大学医学院广西特色生物医药重点实验室,南宁530004

出　　处：《广西医科大学学报》2024年第11期1491-1495,共5页Journal of Guangxi Medical University

基　　金：国家重点研发计划项目资助(No.2022YFA1103901);国家自然科学基金项目资助(No.82372944)。

摘　　要：免疫逃逸是肿瘤的基本特征之一,而免疫疗法近年来在肿瘤治疗中取得了巨大成功。这些疗法包括免疫检查点抑制剂、过继性细胞疗法[如嵌合抗原受体T细胞疗法(CAR-T)和肿瘤浸润淋巴细胞(TIL)]、癌症疫苗、溶瘤病毒等。细胞疗法在多种血液肿瘤中疗效显著,但在实体肿瘤的治疗中效果并不理想,主要原因是回输的免疫细胞难以充分浸润到肿瘤部位。为解决这一难题,研究者尝试将肿瘤组织内的癌细胞原位重编程为免疫细胞,从而充分激活抗肿瘤免疫反应并克服以往细胞治疗依赖体外细胞扩增的局限,同时具有免疫排斥反应弱的优点。目前,肿瘤原位重编程的目标细胞包括巨噬细胞、粒细胞、树突状细胞(DC)和T细胞等,其中树突状细胞作为经典抗原呈递细胞(APC)在启动免疫反应中发挥核心作用,是增强抗肿瘤免疫应答的关键效应细胞。迄今有两种原位重编程的方法,即基于转录因子异位表达及共刺激信号分子和细胞因子共表达策略,均显示出较强的转化应用前景。Immune evasion is one of the fundamental characteristics of tumors,while immunotherapy has achieved significant success in cancer treatment in recent years.These therapies include immune checkpoint inhibitors,adoptive cell therapies[such as chimeric antigen receptor T cell therapy(CAR-T)and tumor-infiltrating lymphocytes(TIL)],cancer vaccines,and oncolytic viruses.Cell therapies have shown remarkable efficacy in various hematologic cancers,but their effect in solid tumors remains suboptimal,primarily due to the difficulty of infused immune cells in sufficiently infiltrating the tumor site.To address this challenge,researchers have explored strategies to reprogram tumor cells in situ within the tumor microenvironment into immune cells,so as to fully activate anti-tumor immune responses and overcome the limitations of conventional cell therapies that rely on in vitro cell expansion.This approach also offers the advantage of a weak immune rejection response.Currently,the target cells for in situ reprogramming include macrophages,granulocytes,dendritic cells(DCs),and T cells,among which dendritic cells,as classic antigen-presenting cells(APCs),play a central role in initiating immune responses and are key effectors in enhancing anti-tumor immunity.To date,two strategies for in situ reprogramming have been explored:one based on the ectopic expression of transcription factors and co-stimulatory molecules,and the other utilizing the co-expression of cytokines,both showing promising prospects for translational application.

关 键 词：抗肿瘤免疫 肿瘤细胞重编程 抗原呈递 树突状细胞 

分 类 号：R73[医药卫生—肿瘤]