中文摘要：

樹突狀細(xì)胞（DCs）被認(rèn)為是腫瘤微環(huán)境（TME）中的主要抗原呈遞細(xì)胞（APCs），通過主要組織相容性復(fù)合體II類（MHC-II）協(xié)調(diào)T細(xì)胞應(yīng)答。然而，腫瘤相關(guān)巨噬細(xì)胞（TAMs）在TME中對(duì)抗原呈遞的貢獻(xiàn)仍很大程度上未被探索。通過整合10種癌癥類型的單細(xì)胞RNA測(cè)序數(shù)據(jù)，我們發(fā)現(xiàn)腫瘤富集的TAMs普遍表現(xiàn)出增強(qiáng)的吞噬作用和MHC-II介導(dǎo)的抗原呈遞，這不同于經(jīng)典的促腫瘤M2巨噬細(xì)胞。值得注意的是，MHC-II高表達(dá)TAMs在多種癌癥中優(yōu)先與調(diào)節(jié)性T細(xì)胞（Tregs）相互作用。利用肺腺癌小鼠模型，我們證明MHC-II高表達(dá)TAMs通過抗原呈遞和直接接觸促進(jìn)Treg活化和擴(kuò)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(shù)據(jù)集顯示，MHC-II高表達(dá)TAMs的存在與免疫治療耐藥相關(guān)。總之，這些發(fā)現(xiàn)重新定義了TME中的巨噬細(xì)胞抗原呈遞，并揭示了新的治療機(jī)會(huì)。

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(shí)間期卷：Volume 45, Issue 4, 117230

Doi：10.1016/j.celrep.2026.117230External Link

產(chǎn)品信息：

貨號(hào)：C-002

規(guī)格：2ml

品牌：Liposoma

產(chǎn)地：荷蘭

名稱：Clodronate Liposomes氯膦酸鹽脂質(zhì)體

辦事處：靶點(diǎn)科技

Clodronate Liposomes氯膦酸鹽脂質(zhì)體清除肺泡巨噬細(xì)胞小鼠肺腺癌模型，荷蘭Liposoma巨噬細(xì)胞清除劑ClodronateLiposomes見刊于Cell Reports：泛癌巨噬細(xì)胞圖譜揭示，MHC-II^high 腫瘤相關(guān)巨噬細(xì)胞（TAMs）通過物理相互作用誘導(dǎo)調(diào)節(jié)性T細(xì)胞（Treg）活化。

Liposoma巨噬細(xì)胞清除劑Clodronate Liposomes氯膦酸二鈉脂質(zhì)體清除巨噬細(xì)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(xì)胞清除材料和方法文獻(xiàn)截圖：