中文摘要:
樹突狀細胞(DCs)被認為是腫瘤微環境(TME)中的主要抗原呈遞細胞(APCs),通過主要組織相容性復合體II類(MHC-II)協調T細胞應答。然而,腫瘤相關巨噬細胞(TAMs)在TME中對抗原呈遞的貢獻仍很大程度上未被探索。通過整合10種癌癥類型的單細胞RNA測序數據,我們發現腫瘤富集的TAMs普遍表現出增強的吞噬作用和MHC-II介導的抗原呈遞,這不同于經典的促腫瘤M2巨噬細胞。值得注意的是,MHC-II高表達TAMs在多種癌癥中優先與調節性T細胞(Tregs)相互作用。利用肺腺癌小鼠模型,我們證明MHC-II高表達TAMs通過抗原呈遞和直接接觸促進Treg活化和擴增,而清除它們則抑制Treg活化并抑制腫瘤生長。此外,接受免疫治療患者的臨床數據集顯示,MHC-II高表達TAMs的存在與免疫治療耐藥相關。總之,這些發現重新定義了TME中的巨噬細胞抗原呈遞,并揭示了新的治療機會。
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.
論文信息:
論文題目:Pan-cancer macrophage atlas uncovers that MHC-IIhigh TAMs induce Treg activation through physical interactions
期刊名稱:Cell Reports
時間期卷:Volume 45, Issue 4, 117230
Doi:10.1016/j.celrep.2026.117230External Link
產品信息:
貨號:C-002
規格:2ml
品牌:Liposoma
產地:荷蘭
名稱:Clodronate Liposomes氯膦酸鹽脂質體
辦事處:靶點科技
Clodronate Liposomes氯膦酸鹽脂質體清除肺泡巨噬細胞小鼠肺腺癌模型,荷蘭Liposoma巨噬細胞清除劑ClodronateLiposomes見刊于Cell Reports:泛癌巨噬細胞圖譜揭示,MHC-II^high 腫瘤相關巨噬細胞(TAMs)通過物理相互作用誘導調節性T細胞(Treg)活化。

Liposoma巨噬細胞清除劑Clodronate Liposomes氯膦酸二鈉脂質體清除巨噬細胞的材料和方法:
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.
巨噬細胞清除材料和方法文獻截圖:

