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Ablation of ERO1A induces lethal endoplasmic reticulum stress responses and immunogenic cell death to activate anti-tumor immunity
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- Liu, Lihui (author)
- Chinese Acad Med Sci & Peking Union Med Coll, Natl Canc Ctr, Natl Clin Res Ctr Canc, State Key Lab Mol Oncol,Canc Hosp,Dept Med Oncol, Beijing 100021, Peoples R China.;Chinese Acad Med Sci & Peking Union Med Coll, Natl Clin Res Ctr Canc, CAMS Key Lab Translat Res Lung Canc,Canc Hosp, State Key Lab Mol Oncol,Dept Med Oncol,Natl Canc C, Beijing 100021, Peoples R China.
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- Li, Sini (author)
- Chinese Acad Med Sci & Peking Union Med Coll, Natl Canc Ctr, Natl Clin Res Ctr Canc, State Key Lab Mol Oncol,Canc Hosp,Dept Med Oncol, Beijing 100021, Peoples R China.;Chinese Acad Med Sci & Peking Union Med Coll, Natl Clin Res Ctr Canc, CAMS Key Lab Translat Res Lung Canc,Canc Hosp, State Key Lab Mol Oncol,Dept Med Oncol,Natl Canc C, Beijing 100021, Peoples R China.;Chinese Acad Sci, Zhejiang Canc Hosp, Hangzhou Inst Med HIM, Dept Med Thorac Oncol, Hangzhou 310022, Zhejiang, Peoples R China.
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- Qu, Yan (author)
- Chinese Acad Med Sci & Peking Union Med Coll, Natl Canc Ctr, Natl Clin Res Ctr Canc, State Key Lab Mol Oncol,Canc Hosp,Dept Med Oncol, Beijing 100021, Peoples R China.;Chinese Acad Med Sci & Peking Union Med Coll, Natl Clin Res Ctr Canc, CAMS Key Lab Translat Res Lung Canc,Canc Hosp, State Key Lab Mol Oncol,Dept Med Oncol,Natl Canc C, Beijing 100021, Peoples R China.;Shandong First Med Univ, Dept Radiotherapy, Shandong Prov Hosp, Jinan 250021, Shandong, Peoples R China.;Sichuan Univ, West China Hosp, Canc Ctr, Chengdu 610041, Sichuan, Peoples R China.
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- Chinese Acad Med Sci & Peking Union Med Coll, Natl Canc Ctr, Natl Clin Res Ctr Canc, State Key Lab Mol Oncol,Canc Hosp,Dept Med Oncol, Beijing 100021, Peoples R China;Chinese Acad Med Sci & Peking Union Med Coll, Natl Clin Res Ctr Canc, CAMS Key Lab Translat Res Lung Canc,Canc Hosp, State Key Lab Mol Oncol,Dept Med Oncol,Natl Canc C, Beijing 100021, Peoples R China. Chinese Acad Med Sci & Peking Union Med Coll, Natl Canc Ctr, Natl Clin Res Ctr Canc, State Key Lab Mol Oncol,Canc Hosp,Dept Med Oncol, Beijing 100021, Peoples R China.;Chinese Acad Med Sci & Peking Union Med Coll, Natl Clin Res Ctr Canc, CAMS Key Lab Translat Res Lung Canc,Canc Hosp, State Key Lab Mol Oncol,Dept Med Oncol,Natl Canc C, Beijing 100021, Peoples R China.;Chinese Acad Sci, Zhejiang Canc Hosp, Hangzhou Inst Med HIM, Dept Med Thorac Oncol, Hangzhou 310022, Zhejiang, Peoples R China. (creator_code:org_t)
- Cell Press, 2023
- 2023
- English.
- In: Cell Reports Medicine. - : Cell Press. - 2666-3791. ; 4:10
- Journal article (peer-reviewed)
Abstract
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- Immunophenotyping of the tumor microenvironment (TME) is essential for enhancing immunotherapy effi-cacy. However, strategies for characterizing the TME exhibit significant heterogeneity. Here, we show that endoplasmic reticular oxidoreductase-1a (ERO1A) mediates an immune-suppressive TME and attenuates the response to PD-1 blockade. Ablation of ERO1A in tumor cells substantially incites anti-tumor T cell im-munity and promotes the efficacy of aPD-1 in therapeutic models. Single-cell RNA-sequencing analyses confirm that ERO1A correlates with immunosuppression and dysfunction of CD8+ T cells along anti-PD-1 treatment. In human lung cancer, high ERO1A expression is associated with a higher risk of recurrence following neoadjuvant immunotherapy. Mechanistically, ERO1A ablation impairs the balance between IRE1a and PERK signaling activities and induces lethal unfolded protein responses in tumor cells undergoing endoplasmic reticulum stress, thereby enhancing anti-tumor immunity via immunogenic cell death. These findings reveal how tumor ERO1A induces immunosuppression, highlighting its potential as a therapeutic target for cancer immunotherapy.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
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- art (subject category)
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- Liu, Lihui
- Li, Sini
- Qu, Yan
- Bai, Hua
- Pan, Xiangyu
- Wang, Jian
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- Wang, Zhijie
- Duan, Jianchun
- Zhong, Jia
- Wan, Rui
- Fei, Kailun
- Xu, Jiachen
- Yuan, Li
- Wang, Chao
- Xue, Pei
- Zhang, Xue
- Ma, Zixiao
- Wang, Jie
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