技术文章您现在的位置:首页 > 技术文章 > 泛癌巨噬细胞图谱揭示,MHC-II^high 肿瘤相关巨噬细胞(TAMs)通过物理相互作用诱导调节性T细胞(Treg)活化。

泛癌巨噬细胞图谱揭示,MHC-II^high 肿瘤相关巨噬细胞(TAMs)通过物理相互作用诱导调节性T细胞(Treg)活化。

更新时间:2026-09-28   点击次数:29次

中文摘要:

树突状细胞(DCs)被认为是肿瘤微环境(TME)中的主要抗原呈递细胞(APCs),通过主要组织相容性复合体II类(MHC-II)协调T细胞应答。然而,肿瘤相关巨噬细胞(TAMs)在TME中对抗原呈递的贡献仍很大程度上未被探索。通过整合10种癌症类型的单细胞RNA测序数据,我们发现肿瘤富集的TAMs普遍表现出增强的吞噬作用和MHC-II介导的抗原呈递,这不同于经典的促肿瘤M2巨噬细胞。值得注意的是,MHC-II高表达TAMs在多种癌症中优先与调节性T细胞(Tregs)相互作用。利用肺腺癌小鼠模型,我们证明MHC-II高表达TAMs通过抗原呈递和直接接触促进Treg活化和扩增,而清除它们则抑制Treg活化并抑制肿瘤生长。此外,接受免疫治疗患者的临床数据集显示,MHC-II高表达TAMs的存在与免疫治疗耐药相关。总之,这些发现重新定义了TME中的巨噬细胞抗原呈递,并揭示了新的治疗机会。


英文摘要:

Dendritic cells (DCs) are recognized as the primary antigen-presenting cells (APCs) within the tumor microenvironment (TME), orchestrating T cell responses via the major histocompatibility complex class II (MHC-II). However, the contribution of tumor-associated macrophages (TAMs) to antigen presentation within the TME remains largely unexplored. By integrating single-cell RNA-seq data from 10 cancer types, we discover that tumor-enriched TAMs universally exhibit elevated phagocytosis and MHC-II-mediated antigen presentation, distinct from canonical tumor-promoting M2 macrophages. Notably, MHC-IIhigh TAMs preferentially interact with regulatory T cells (Tregs) across cancers. Using a mouse model of lung adenocarcinoma, we demonstrate that MHC-IIhigh TAMs promote Treg activation and expansion through antigen presentation and direct contact, while their depletion restrains Treg activation and suppresses tumor growth. Moreover, clinical datasets from patients receiving immunotherapy reveal that the presence of MHC-IIhigh TAMs correlates with immunotherapy resistance. Together, these findings redefine macrophage antigen presentation in the TME and reveal new therapeutic opportunities.


论文信息:

论文题目:Pan-cancer macrophage atlas uncovers that MHC-IIhigh TAMs induce Treg activation through physical interactions

期刊名称:Cell Reports

时间期卷:Volume 45, Issue 4, 117230

在线时间:2026年4月28日

Doi:10.1016/j.celrep.2026.117230External Link

产品信息:

货号:C-002

规格:2ml

品牌:Liposoma

产地:荷兰

名称:Clodronate Liposomes氯膦酸盐脂质体

办事处:靶点科技


Clodronate Liposomes氯膦酸盐脂质体清除肺泡巨噬细胞小鼠肺腺癌模型,荷兰Liposoma巨噬细胞清除剂ClodronateLiposomes见刊于Cell Reports:泛癌巨噬细胞图谱揭示,MHC-II^high 肿瘤相关巨噬细胞(TAMs)通过物理相互作用诱导调节性T细胞(Treg)活化。

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Liposoma巨噬细胞清除剂Clodronate Liposomes氯膦酸二钠脂质体清除巨噬细胞的材料和方法:

In vivo macrophage depletion

Depletion of alveolar macrophages was achieved by intranasal instillation of clodronate liposomes (Liposoma, Cat# C-002). Owing to their high phagocytic activity, alveolar macrophages internalize the liposomes, resulting in intracellular release of clodronate and subsequent apoptotic cell death. Mice were anesthetized and administered 40 μL clodronate liposomes per mouse via nasal instillation every three days according to the experimental schedule. Control mice received equal volumes of PBS when applicable.



巨噬细胞清除材料和方法文献截图:

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