IRE1α silences dsRNA to prevent taxane-induced pyroptosis in triple-negative breast cancer.

Autor:	Xu L; Department of Experimental Therapeutics, James P. Allison Institute, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA., Peng F; Department of Molecular and Cellular Biology, Lester and Sue Smith Breast Center, Dun L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA., Luo Q; Department of Experimental Therapeutics, James P. Allison Institute, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA., Ding Y; Department of Experimental Therapeutics, James P. Allison Institute, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA., Yuan F; Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX 77030, USA., Zheng L; Therapeutic Innovation Center (THINC), and Marrs McLean Department of Biochemistry and Molecular Pharmacology, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA., He W; Department of Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Zhang SS; Department of Chemistry, Rice University, Houston, TX 77005, USA., Fu X; Department of Pathology, Xijing Hospital, Xi'an, Shaanxi 710032, China., Liu J; Department of Pathology, Xijing Hospital, Xi'an, Shaanxi 710032, China., Mutlu AS; Therapeutic Innovation Center (THINC), and Marrs McLean Department of Biochemistry and Molecular Pharmacology, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA., Wang S; Department of Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Nehring RB; Therapeutic Innovation Center (THINC), and Marrs McLean Department of Biochemistry and Molecular Pharmacology, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA., Li X; College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, Sichuan 611130, China., Tang Q; College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, Sichuan 611130, China., Li C; Department of Experimental Therapeutics, James P. Allison Institute, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA., Lv X; Department of Experimental Therapeutics, James P. Allison Institute, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA., Dobrolecki LE; Department of Molecular and Cellular Biology, Lester and Sue Smith Breast Center, Dun L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA., Zhang W; Department of Molecular and Cellular Biology, Lester and Sue Smith Breast Center, Dun L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA., Han D; Department of Molecular and Cellular Biology, Lester and Sue Smith Breast Center, Dun L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA., Zhao N; Department of Molecular and Cellular Biology, Lester and Sue Smith Breast Center, Dun L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA., Jaehnig E; Department of Molecular and Cellular Biology, Lester and Sue Smith Breast Center, Dun L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA., Wang J; Department of Molecular and Cellular Biology, Lester and Sue Smith Breast Center, Dun L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA., Wu W; Department of Experimental Therapeutics, James P. Allison Institute, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA., Graham DA; Department of Molecular and Cellular Biology, Lester and Sue Smith Breast Center, Dun L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA., Li Y; Therapeutic Innovation Center (THINC), and Marrs McLean Department of Biochemistry and Molecular Pharmacology, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA., Chen R; Therapeutic Innovation Center (THINC), and Marrs McLean Department of Biochemistry and Molecular Pharmacology, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA., Peng W; Department of Biology and Biochemistry, University of Houston, Houston, TX 77204, USA., Chen Y; Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Catic A; Department of Molecular and Cellular Biology, Lester and Sue Smith Breast Center, Dun L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA., Zhang Z; Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Zhang B; Department of Molecular and Cellular Biology, Lester and Sue Smith Breast Center, Dun L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA., Mustoe AM; Therapeutic Innovation Center (THINC), and Marrs McLean Department of Biochemistry and Molecular Pharmacology, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA., Koong AC; Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Miles G; Department of Molecular and Cellular Biology, Lester and Sue Smith Breast Center, Dun L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA., Lewis MT; Department of Molecular and Cellular Biology, Lester and Sue Smith Breast Center, Dun L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA., Wang MC; HHMI Janelia Research Campus, Ashburn, VA 20147, USA., Rosenberg SM; Therapeutic Innovation Center (THINC), and Marrs McLean Department of Biochemistry and Molecular Pharmacology, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA., O'Malley BW; Department of Molecular and Cellular Biology, Lester and Sue Smith Breast Center, Dun L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA., Westbrook TF; Therapeutic Innovation Center (THINC), and Marrs McLean Department of Biochemistry and Molecular Pharmacology, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA., Xu H; Department of Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA., Zhang XH; Department of Molecular and Cellular Biology, Lester and Sue Smith Breast Center, Dun L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA., Osborne CK; Department of Molecular and Cellular Biology, Lester and Sue Smith Breast Center, Dun L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA., Li JB; Department of Genetics, Stanford University, Stanford, CA 94305, USA., Ellis MJ; Department of Molecular and Cellular Biology, Lester and Sue Smith Breast Center, Dun L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA., Rimawi MF; Department of Molecular and Cellular Biology, Lester and Sue Smith Breast Center, Dun L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA., Rosen JM; Department of Molecular and Cellular Biology, Lester and Sue Smith Breast Center, Dun L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA., Chen X; Department of Experimental Therapeutics, James P. Allison Institute, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA; Department of Molecular and Cellular Biology, Lester and Sue Smith Breast Center, Dun L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA. Electronic address: xchen23@mdanderson.org.
Jazyk:	angličtina
Zdroj:	Cell [Cell] 2024 Oct 14. Date of Electronic Publication: 2024 Oct 14.
DOI:	10.1016/j.cell.2024.09.032
Abstrakt:	Chemotherapy is often combined with immune checkpoint inhibitor (ICIs) to enhance immunotherapy responses. Despite the approval of chemo-immunotherapy in multiple human cancers, many immunologically cold tumors remain unresponsive. The mechanisms determining the immunogenicity of chemotherapy are elusive. Here, we identify the ER stress sensor IRE1α as a critical checkpoint that restricts the immunostimulatory effects of taxane chemotherapy and prevents the innate immune recognition of immunologically cold triple-negative breast cancer (TNBC). IRE1α RNase silences taxane-induced double-stranded RNA (dsRNA) through regulated IRE1-dependent decay (RIDD) to prevent NLRP3 inflammasome-dependent pyroptosis. Inhibition of IRE1α in Trp53 -/- TNBC allows taxane to induce extensive dsRNAs that are sensed by ZBP1, which in turn activates NLRP3-GSDMD-mediated pyroptosis. Consequently, IRE1α RNase inhibitor plus taxane converts PD-L1-negative, ICI-unresponsive TNBC tumors into PD-L1 high immunogenic tumors that are hyper-sensitive to ICI. We reveal IRE1α as a cancer cell defense mechanism that prevents taxane-induced danger signal accumulation and pyroptotic cell death. Competing Interests: Declaration of interests M.F.R. receives research funding from Pfizer and Genentech and consulting fees from Novartis, Seagen, Macrogenics, and AstraZeneca. M.F.R. is the PI of clinical trial NCT03950570. X.C. reports previous research funding from Fosun Pharma. M.J.E. holds patents and receives income from Veracyte on the PAM50-based products, Prosigna. (Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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