ID1 expressing macrophages support cancer cell stemness and limit CD8(+) T cell infiltration in colorectal cancer.
ID1 expressing macrophages support cancer cell stemness and limit CD8(+) T cell infiltration in colorectal cancer.
复制标题
表达ID1的巨噬细胞支持癌细胞干细胞性并限制结直肠癌中的CD8（+）T细胞浸润。
DOI：
10.1038/s41467-023-43548-w
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发表时间：
2023-11-23
影响因子：
16.6
通讯作者：
Hua, Fang
中科院分区：
文献类型：
--
作者：
Shang, Shuang;Yang, Chen;Chen, Fei;Xiang, Ren-shen;Zhang, Huan;Dai, Shu-yuan;Liu, Jing;Lv, Xiao-xi;Zhang, Cheng;Liu, Xiao-tong;Zhang, Qi;Lu, Shuai-bing;Song, Jia-wei;Yu, Jiao-jiao;Zhou, Ji-chao;Zhang, Xiao-wei;Cui, Bing;Li, Ping-ping;Zhu, Sheng-tao;Zhang, Hai-zeng;Hua, Fang
消除肿瘤干细胞（CSCs）和恢复抗肿瘤免疫仍然是癌症治疗中未遇到的挑战。肿瘤相关巨噬细胞（tumor -associated macrophages, tam）是肿瘤组织中重要的免疫细胞群，有助于形成CSC壁龛和抑制性免疫微环境。在这里，我们报告了TAMs中分化抑制因子1 （ID1）的高表达与结直肠癌（CRC）患者的不良预后相关。表达ID1的巨噬细胞维持肿瘤的干细胞性，抑制CD8+ T细胞的浸润。在机制上，ID1与STAT1相互作用诱导其细胞质分布，并抑制STAT1介导的SerpinB2和CCL4转录，这两种分泌因子负责肿瘤干细胞抑制和CD8+ T细胞募集。减少ID1表达可改善结直肠癌的进展，增强肿瘤对免疫治疗和化疗的敏感性。总之，我们的研究强调了ID1在控制tam的肿瘤表型中的关键作用，并为ID1在CRC中的治疗靶向铺平了道路。分化抑制剂1 （ID1）被认为是一种促癌因子，也参与了免疫抑制肿瘤微环境的形成。本文作者报道，表达id1的肿瘤相关巨噬细胞通过促进癌细胞干性和CD8+ T细胞排斥来促进结直肠癌的进展。
Elimination of cancer stem cells (CSCs) and reinvigoration of antitumor immunity remain unmet challenges for cancer therapy. Tumor-associated macrophages (TAMs) constitute the prominant population of immune cells in tumor tissues, contributing to the formation of CSC niches and a suppressive immune microenvironment. Here, we report that high expression of inhibitor of differentiation 1 (ID1) in TAMs correlates with poor outcome in patients with colorectal cancer (CRC). ID1 expressing macrophages maintain cancer stemness and impede CD8+ T cell infiltration. Mechanistically, ID1 interacts with STAT1 to induce its cytoplasmic distribution and inhibits STAT1-mediated SerpinB2 and CCL4 transcription, two secretory factors responsible for cancer stemness inhibition and CD8+ T cell recruitment. Reducing ID1 expression ameliorates CRC progression and enhances tumor sensitivity to immunotherapy and chemotherapy. Collectively, our study highlights the pivotal role of ID1 in controlling the protumor phenotype of TAMs and paves the way for therapeutic targeting of ID1 in CRC. Inhibitor of differentiation 1 (ID1) has been described as a cancer-promoting factor and also involved in the formation of an immunosuppressive tumor microenvironment. Here the authors report that ID1-expressing tumor associated macrophages favor colorectal cancer progression by promoting cancer cell stemness and CD8+ T cell exclusion.
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影响因子：
64.5
作者：
BENEZRA, R;DAVIS, RL;WEINTRAUB, H
通讯作者：
WEINTRAUB, H
DOI：
10.1038/s41573-022-00520-5
发表时间：
2022-11
期刊：
Nature reviews. Drug discovery
影响因子：
--
作者：
通讯作者：
--
影响因子：
50.3
作者：
Cassetta, Luca;Fragkogianni, Stamatina;Pollard, Jeffrey W.
通讯作者：
Pollard, Jeffrey W.
影响因子：
4
作者：
Dehnel, Nathalie;Moral, Javier;Bruenet, Bernhard
通讯作者：
Bruenet, Bernhard
DOI：
10.1186/s10020-021-00383-3
发表时间：
2021-09-28
期刊：
Molecular medicine (Cambridge, Mass.)
影响因子：
--
作者：
Allavena P;Digifico E;Belgiovine C
通讯作者：
Belgiovine C