肿瘤免疫治疗新视角:RUNX的作用与意义

A new perspective on tumor immunotherapy:the role and significance of RUNX

RUNX属于转录因子家族,是哺乳动物发育过程中不可或缺的调控因子,在哺乳动物的细胞增殖、分化、谱系发育、成骨和神经形成中发挥重要作用。围绕RUNX的研究已揭示了其功能的多样性以及在肿瘤发生发展过程中的功能。RUNX家族成员在不同类型的肿瘤中具有不一的作用,与肿瘤微环境中的各组分也有不同程度的关联。RUNX家族成员可以调节肿瘤微环境中CD4+辅助性T(Th)细胞和CD8+细胞毒性T细胞(CTL)的谱系发育分化,调控组织驻留T淋巴细胞的表型、分化和存活,驱动NK细胞的增殖活化和组织驻留。RUNX家族缺失会导致MDSC的增殖和成熟活化,从而诱导肿瘤免疫抑制微环境的产生。RUNX家族成员的表达也与肿瘤微环境中肿瘤相关成纤维细胞(CAF)的浸润程度、不同免疫细胞的浸润、免疫检查点基因表达和药物敏感性显著相关,它们可作为潜在的肿瘤预后标志物和免疫治疗靶点,与CAR-T细胞疗法的联用具有很大的应用前景。本文从RUNX的基本结构和功能研究及其参与调控肿瘤免疫和微环境中各类组分的作用进展进行综述,旨在为未来以RUNX为主要靶点的肿瘤免疫治疗提供新的视角。

RUNX,a member of transcription factor family,plays an important role in the regulation of mammalian cell proliferation,differentiation,lineage development,osteogenesis and neurogenesis.The studies of RUNX have revealed the diversity of its function and its role in tumor genesis and progression.RUNX family members have different functional manifestations in different types of tumors and have different levels of association with various components in the tumor microenvironment.RUNX family members regulate the lineage development and differentiation of CD4+helper T(Th)cells and CD8+cytotoxic T lymphocytes(CTLs)in the tumor microenvironment,modulate the phenotype,differentiation,and survival of tissue-resident T-lymphocytes,and drive the proliferation activation and tissue-resident of NK-cells.RUNX family deletion leads to MDSC proliferation and maturation activation,which induces a tumor immunosuppressive microenvironment.The expression of RUNX family members also significantly correlates with the degree of infiltration of tumor-associated fibroblasts(CAFs)in the tumor microenvironment,the infiltration of different immune cells,immune checkpoint gene expression,and drug sensitivity,which could serve as potential prognostic markers of tumors and as targets for tumor immunotherapy,and the combination with CAR-T cell therapy has great potential for application.This review focuses on the basic structure and function of RUNX and its role in the regulation of various components in tumor immunity and microenvironment,aiming to provide a new perspective for tumor immunotherapy with RUNX as the main target in the future.