抗体寡链核苷酸耦联策略在肿瘤相关巨噬细胞极化调控中的应用研究  

Application of antibody oligostranded nucleotide conjugation strategy in polarization regulation of tumor-associated macrophages

作　　者：马启明 陈炳官[2] 韩俊毅[2] Ma Qiming;Chen Bingguan;Han Junyi(School of Medicine,Tongji University,Shanghai 200092,China;Department of Gastrointestinal Surgery,East Hospital Affiliated To Tongji University,Shanghai 200120,China)

机构地区：[1]同济大学医学院,上海200092 [2]上海市东方医院胃肠外科,上海200120

出　　处：《中华实验外科杂志》2024年第5期1099-1105,共7页Chinese Journal of Experimental Surgery

基　　金：国家自然科学基金(8216110877);上海市浦东新区卫生系统特色专病建设资助(PWZzb2022-06)。

摘　　要：肿瘤的发生与发展是肿瘤细胞与其肿瘤微环境(TME)相互作用的结果,TME分布着多种基质细胞,其中以肿瘤相关巨噬细胞(TAMs)最为丰富.根据巨噬细胞与其发生应答反应的辅助性T细胞类型,可大致将极化的巨噬细胞分为M1型和M2型巨噬细胞.在多数肿瘤中,M1型巨噬细胞参与抗肿瘤免疫,而M2型巨噬细胞主要发挥促肿瘤作用并与患者的不良预后相关.最近的研究表明,在肿瘤发展过程中,TAMs经历了从免疫刺激的M1样表型到免疫抑制的M2样表型的过程,该过程受多种因素影响并且可被逆转.这为肿瘤的免疫治疗提供了一种新思路,即通过TAMs的定向调控,逆转M2样巨噬细胞促肿瘤的微环境,发挥M1样巨噬细胞对肿瘤的抑制作用.该方案还有望与免疫检查点阻断(ICB)联用,增强ICB的治疗效果.小干扰RNA(siRNA)介导的基因沉默是一种安全可用于人类的基因调控方式,对TAMs的调控有得天独厚的优势;特异性抗体因其高选择性已被广泛应用于多种肿瘤的靶向治疗.抗体-寡核苷酸结合物(AOCs)正是结合了两者的优势,是实现TAMs中M2样巨噬细胞逆转的最佳方式.本文主要就TME中TAMs的作用及其调节机制进行综述,并探讨应用AOCs对TAMs表型进行定向调控,抑制肿瘤发展的可行性和应用前景.The occurrence and development of tumors is the result of the interaction between tumor cells and their tumor micro environment(TME),which distributes a variety of stromal cells,among which tumor-associated macrophages(TAMs)are the most abundant.According to the type of helper T cells with which macrophages respond,polarized macrophages can be roughly divided into M1 and M2 macrophages.In most tumors,M1 macrophages are involved in anti-tumor immunity,while M2 macrophages mainly play a pro-tumor role and are associated with poor prognosis.Recent studies have shown that during tumor development,TAMs undergo a process from an immunostimulated M1-like phenotype to an immunosuppressive M2-like phenotype,which is influenced by a variety of factors and can be reversed.This provides a new idea for tumor immunotherapy,that is,through the directional regulation of TAMs,the microenvironment of M2-like macrophages to promote tumors is reversed,and the inhibitory effect of M1-like macrophages on tumors is exerted.The regimen is also expected to be used in combination with immune checkpoint blockade(ICB)to enhance the therapeutic effect of ICB.siRNA-mediated gene silencing is a safe gene regulation method for humans,and has unique advantages in the regulation of TAMs.Specific antibodies have been widely used in targeted therapy for a variety of tumors due to their high selectivity.The antibody-oligonucleotide conjugates(AOCs)combine the advantages of both and are the best way to reverse M2-like macrophages in TAMs.This article mainly reviews the role and regulatory mechanism of TAMs in TME,and discusses the feasibility and application prospect of using AOC drugs to target the phenotype of TAMs and inhibit tumor development.

关 键 词：肿瘤微环境 巨噬细胞 抗体-寡核苷酸结合物 免疫治疗 

分 类 号：R730[医药卫生—肿瘤]