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科学家发现靶向TREM2可增强抗PD1免疫治疗
作者:小柯机器人 发布时间:2020/8/13 15:55:24

美国华盛顿大学医学院Marco Colonna小组在研究中取得进展。他们的最新研究揭示TREM2重塑肿瘤骨髓细胞构成,这有利于增强抗PD-1免疫疗法。相关论文于2020年8月11日在线发表在《细胞》杂志上。

在本研究中,研究人员发现与野生型小鼠相比,Trem2 –/–小鼠对各种癌症的生长更有抵抗力,并且对抗PD-1免疫疗法的反应更敏感。

此外,抗TREM2 mAb与抗PD-1联合使用可以抑制肿瘤生长并促进肿瘤消退。scRNA-seq表明,TREM2缺失和抗TREM2均与肿瘤浸润过程中MRC1+和CX3CR1+巨噬细胞缺乏有关,并与表达可改善T细胞反应免疫刺激因子的髓样细胞亚群同时扩增。TREM2在200多种癌症患者的肿瘤巨噬细胞中表达,并且与两类癌症的生存期延长呈负相关。因此,TREM2可作为改善肿瘤髓系细胞浸润性并增强检查点免疫治疗的靶点。

据介绍,检查点免疫疗法释放了针对肿瘤的T细胞,但该方法受到免疫抑制性髓样细胞的破坏。TREM2是一种髓样受体,在阿尔茨海默氏病患者小胶质细胞中传递维持细胞反应的细胞内信号。肿瘤浸润性巨噬细胞也表达TREM2。

附:英文原文

Title: TREM2 Modulation Remodels the Tumor Myeloid Landscape Enhancing Anti-PD-1 Immunotherapy

Author: Martina Molgora, Ekaterina Esaulova, William Vermi, Jinchao Hou, Yun Chen, Jingqin Luo, Simone Brioschi, Mattia Bugatti, Andrea Salvatore Omodei, Biancamaria Ricci, Catrina Fronick, Santosh K. Panda, Yoshiko Takeuchi, Matthew M. Gubin, Roberta Faccio, Marina Cella, Susan Gilfillan, Emil R. Unanue, Maxim N. Artyomov, Robert D. Schreiber, Marco Colonna

Issue&Volume: 2020-08-11

Abstract: Checkpoint immunotherapy unleashes T cell control of tumors, but is undermined byimmunosuppressive myeloid cells. TREM2 is a myeloid receptor that transmits intracellularsignals that sustain microglial responses during Alzheimer’s disease. TREM2 is alsoexpressed by tumor-infiltrating macrophages. Here, we found that Trem2–/– mice are more resistant to growth of various cancers than wild-type mice and aremore responsive to anti-PD-1 immunotherapy. Furthermore, treatment with anti-TREM2mAb curbed tumor growth and fostered regression when combined with anti-PD-1. scRNA-seqrevealed that both TREM2 deletion and anti-TREM2 are associated with scant MRC1+ and CX3CR1+ macrophages in the tumor infiltrate, paralleled by expansion of myeloid subsets expressingimmunostimulatory molecules that promote improved T cell responses. TREM2 was expressedin tumor macrophages in over 200 human cancer cases and inversely correlated withprolonged survival for two types of cancer. Thus, TREM2 might be targeted to modifytumor myeloid infiltrates and augment checkpoint immunotherapy.

DOI: 10.1016/j.cell.2020.07.013

Source: https://www.cell.com/cell/fulltext/S0092-8674(20)30878-3

期刊信息
Cell:《细胞》,创刊于1974年。隶属于细胞出版社,最新IF:36.216
官方网址:https://www.cell.com/