肿瘤相关巨噬细胞（TAM）在肿瘤发展、转移和治疗抵抗中扮演了关键角色。TAM包含两种可相互极化的类型：促炎、抑制肿瘤生长的M1型和抑炎、促进肿瘤进展的M2型。表观遗传机制在肿瘤微环境对TAM的功能塑造中的作用十分独特，主要介导极化相关信号通路、细胞因子、代谢酶、关键转录因子和MHC及其调控因子等功能基因的转录或转录后调控，从而决定TAM的极化状态和功能。因此，从表观调控入手抑制M2极化、促进M1极化，进而引起TAM功能重塑，已逐渐成为肿瘤治疗的一个新兴策略。通过鉴定TAM特异性及关键表观调节机制、开发靶向TAM的新型表观药物递送系统、有效联合其他抗肿瘤疗法等方式，可进一步提高基于表观遗传调控的靶向巨噬细胞治疗的特异性，降低不良反应，实现更理想的抗肿瘤效果。

Tumor-associated macrophages (TAMs), key players in tumor development, metastasis and drug resistance, contain two polarizable phenotypes: inflammatory, tumor-inhibitory M1 type and anti-inflammatory, tumor-promoting M2 type. Epigenetic regulation plays a distinct role in functional programming of TAMs in the tumor microenvironment. It determines the polarization and function of TAMs mainly through mediating transcriptional or post-transcriptional regulation of polarization-related signal pathways, cytokines, metabolic enzymes, key transcription factors, MHC and its regulators. Therefore, epigenetic regulation-based inhibition of M2 polarization and promotion of M1 polarization to induce functional reprogramming of TAMs has gradually developed into a novel strategy in the field of antitumor immunotherapy. Identification of more specific and pivotal mechanisms in epigenetic regulation of TAMs and development of new TAM-targeting epigenetic drug delivery system, combined with other antitumor therapies, might improve targeting specificity of epigenetic regulation of TAMs, reduce adverse effects and achieve better antitumor effects.

R730.51；R730.3

国家自然科学基金面上项目资助（No.82071762）