美国达特茅斯盖泽尔医学院Claudia V. Jakubzick小组的研究显示，趋化因子定义的巨噬细胞生态位建立肿瘤免疫的空间组织。相关论文于2026年3月23日发表于国际顶尖学术期刊《自然—免疫学》杂志上。

在这里，该团队揭示了组织内CD206hi和CD206lo间质巨噬细胞（IM）亚群和Ly6c2⁺Fn1⁺Vcan⁺募集巨噬细胞（recMacs）在肺癌中的分工。利用单细胞和空间转录组学，该课题组确定了具有相反功能的趋化因子表达的IM亚群。Cxcl13⁺CD206^hi IMs、Cxcl9⁺CD206^hi IMs和Cxcl10⁺CD206^hi IMs沿支气管血管区定位，驱动三级淋巴样结构形成、淋巴细胞募集和肿瘤控制，而Ccl2⁺ IMs定位于肿瘤区域，募集致瘤蛋白Ly6c2⁺Fn1⁺Vcan⁺ recMacs。

此外，Ly6C⁺CD11b⁺单核细胞衍生的树突状细胞（moDCs）在肿瘤引流淋巴结中具有免疫抑制抗原呈递细胞的功能。在新抗原接种过程中，用马拉韦洛克阻断CCR5选择性地抑制携带抗原的moDC迁移，增强树突状细胞介导的抗肿瘤免疫。这些发现显示了巨噬细胞谱系和空间区隔化如何控制肿瘤免疫，并确定了在破坏巨噬细胞驱动的免疫抑制的同时保持保护性IM功能的策略。

据介绍，巨噬细胞是实体肿瘤中最丰富的免疫细胞之一，但巨噬细胞的谱系和空间组织如何影响抗肿瘤免疫尚不清楚。

附：英文原文

Title: Chemokine-defined macrophage niches establish spatial organization of tumor immunity

Author: Ghosh, Soubhik, Li, Xin, Rawat, Kavita, Dighal, Aishwarya, Kalinowski, Stephanie, Hosseini, Reza, Kolling, Fred W., Ringelberg, Carol S., Jakubzick, Claudia V.

Issue&Volume: 2026-03-23

Abstract: Macrophages are among the most abundant immune cells in solid tumors, yet how macrophage lineage and spatial organization shape antitumor immunity remains unclear. Here we uncovered a division of labor between tissue-resident CD206hi and CD206lo interstitial macrophage (IM) subsets and Ly6c2+Fn1+Vcan+ recruited macrophages (recMacs) in lung cancer. Using single-cell and spatial transcriptomics, we identified chemokine-expressing IM subsets with opposing functions. Cxcl13+CD206hi IMs, Cxcl9+CD206hi IMs and Cxcl10+CD206hi IMs positioned along bronchovascular regions drove tertiary lymphoid structure formation, lymphocyte recruitment and tumor control, whereas Ccl2+ IMs, localized within tumor regions, recruited protumorigenic Ly6c2+Fn1+Vcan+ recMacs. In addition, Ly6C+CD11b+ monocyte-derived dendritic cells (moDCs) functioned as immunosuppressive antigen-presenting cells in tumor-draining lymph nodes. During neoantigen vaccination, CCR5 blockade with maraviroc selectively inhibited antigen-bearing moDC migration, enhancing dendritic cell-mediated antitumor immunity. These findings showed how macrophage lineage and spatial compartmentalization govern tumor immunity and identified strategies to preserve protective IM functions, while disrupting macrophage-driven immunosuppression.

DOI: 10.1038/s41590-026-02445-2

Source: https://www.nature.com/articles/s41590-026-02445-2