ID1 expressing macrophages support cancer cell stemness and limit CD8+ T cell infiltration in colorectal cancer

Shuang Shang, Chen Yang, Fei Chen, Ren-shen Xiang, Huan Zhang, Shu-yuan Dai, Jing Liu, Xiao-xi Lv, Cheng Zhang, Xiao-tong Liu, Qi Zhang, Shuai-bing Lu, Jia-wei Song, Jiao-jiao Yu, Ji-chao Zhou, Xiao-wei Zhang, Bing Cui, Ping-ping Li, Sheng-tao Zhu, Hai-zeng Zhang () and Fang Hua ()
Additional contact information
Shuang Shang: Chinese Academy of Medical Sciences & Peking Union Medical College
Chen Yang: Chinese Academy of Medical Sciences & Peking Union Medical College
Fei Chen: Chinese Academy of Medical Sciences & Peking Union Medical College
Ren-shen Xiang: Chinese Academy of Medical Sciences and Peking Union Medical College
Huan Zhang: Chinese Academy of Medical Sciences & Peking Union Medical College
Shu-yuan Dai: Chinese Academy of Medical Sciences & Peking Union Medical College
Jing Liu: Chinese Academy of Medical Sciences & Peking Union Medical College
Xiao-xi Lv: Chinese Academy of Medical Sciences & Peking Union Medical College
Cheng Zhang: Chinese Academy of Medical Sciences & Peking Union Medical College
Xiao-tong Liu: Chinese Academy of Medical Sciences & Peking Union Medical College
Qi Zhang: Chinese Academy of Medical Sciences and Peking Union Medical College
Shuai-bing Lu: Chinese Academy of Medical Sciences and Peking Union Medical College
Jia-wei Song: Chinese Academy of Medical Sciences & Peking Union Medical College
Jiao-jiao Yu: Chinese Academy of Medical Sciences & Peking Union Medical College
Ji-chao Zhou: Chinese Academy of Medical Sciences & Peking Union Medical College
Xiao-wei Zhang: Chinese Academy of Medical Sciences & Peking Union Medical College
Bing Cui: Chinese Academy of Medical Sciences & Peking Union Medical College
Ping-ping Li: Chinese Academy of Medical Sciences & Peking Union Medical College
Sheng-tao Zhu: Beijing Friendship Hospital
Hai-zeng Zhang: Chinese Academy of Medical Sciences and Peking Union Medical College
Fang Hua: Chinese Academy of Medical Sciences & Peking Union Medical College

Nature Communications, 2023, vol. 14, issue 1, 1-19

Abstract: Abstract 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.

Date: 2023
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DOI: 10.1038/s41467-023-43548-w

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