[摘 要] 树突状细胞（DC）作为抗肿瘤免疫应答的核心启动者与调控者，已成为肿瘤免疫治疗的重要靶点。DC疫苗等靶向DC的免疫治疗策略在抗肿瘤治疗中展现出独特优势，但仍存在抗原提呈效率不足、免疫抑制微环境抵抗、功能特异性调控困难等瓶颈问题。肿瘤微环境（TME）中的DC存在高度异质性，不同DC亚群在分化发育、免疫调控及效应转归方面呈现复杂的多样性。解析DC亚群的精确表型与功能机制对于开发新型DC靶向性免疫治疗策略具有重要意义。TME中募集的经典DC、浆细胞样DC、单核细胞来源DC能与肿瘤浸润免疫细胞和微环境中的非免疫细胞（包括肿瘤细胞、成纤维细胞、内皮细胞等）相互作用激活抗肿瘤免疫应答，而TME还会通过转录调控、表观遗传调控、代谢重塑等多种方式抑制DC招募和抗原提呈能力，甚至诱导其向耐受性DC转化。值得注意的是，新近发现的富含免疫调节分子的成熟DC具有双向免疫调控作用，其起源路径和免疫调控网络仍有待深入研究。随着单细胞分析与空间组学分析等技术的发展，有望在单细胞分辨率下系统解析DC亚群的功能多样性及其与TME的时空相互作用网络，为开发下一代精准免疫治疗策略提供新靶点和新思路。

[Abstract] Dendritic cells (DCs), as the core initiators and regulators of anti-tumor immune responses, have emerged as important targets in tumor immunotherapy. Immunotherapeutic strategies targeting DCs, such as DC vaccines, have shown unique advantages in anti-tumor treatment. However, several challenges remain, including insufficient antigen presentation efficiency, resistance from the immunosuppressive microenvironment, and difficulties in achieving specific functional modulation. DCs in the tumor microenvironment (TME) exhibit high heterogeneity, and different DC subpopulations show complex diversity in differentiation and development, immune regulation, and effector outcomes. Elucidating the precise phenotypes and functional mechanisms of DC subpopulations is therefore crucial for developing novel DC-targeted immunotherapeutic strategies. In the TME, recruited conventional DCs, plasmacytoid DCs, and monocyte-derived DCs can interact with tumor-infiltrating immune cells and non-immune cells within the TME (including tumor cells, fibroblasts, endothelial cells, etc.) to activate anti-tumor immune responses. However, the TME can suppress DC recruitment and antigen-presenting capabilities through various means, including transcriptional regulation, epigenetic regulation, and metabolic reprogramming, and may even induce their transformation into tolerogenic DCs. Notably, newly discovered mature DCs enriched with immunoregulatory molecules exhibit bidirectional immunoregulatory functions, yet their origins and immune regulatory networks require in-depth research. With the development of single-cell technology and spatial omics, researchers can systematically analyze the functional diversity of DC subpopulations and their spatiotemporal interactions with the TME at single-cell resolution. These approaches are expected to provide new targets and insights for the development of next-generation precision immunotherapeutic strategies.[Key words] tumor microenvironment; dendritic cell subset; tumor; immunotherapy; immune checkpoint blockade therapy; cell-cell communication

[基金项目] 国家自然科学基金（92374115，32571081）