دورية أكاديمية
أعرض في EDS

A GATA4-regulated secretory program suppresses tumors through recruitment of cytotoxic CD8 T cells.

التفاصيل البيبلوغرافية
العنوان: A GATA4-regulated secretory program suppresses tumors through recruitment of cytotoxic CD8 T cells.
المؤلفون: Patel RS; Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.; Department of Genetics, Harvard Medical School, Boston, MA, USA.; Howard Hughes Medical Institute, Chevy Chase, MD, USA.; Scripps Green Hospital, San Diego, CA, USA., Romero R; David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA.; Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Watson EV; Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.; Department of Genetics, Harvard Medical School, Boston, MA, USA.; Howard Hughes Medical Institute, Chevy Chase, MD, USA., Liang AC; Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.; Department of Genetics, Harvard Medical School, Boston, MA, USA.; Howard Hughes Medical Institute, Chevy Chase, MD, USA., Burger M; David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA., Westcott PMK; David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA., Mercer KL; David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA., Bronson RT; Harvard Medical School, Boston, MA, USA., Wooten EC; Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.; Department of Genetics, Harvard Medical School, Boston, MA, USA.; Howard Hughes Medical Institute, Chevy Chase, MD, USA., Bhutkar A; David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA., Jacks T; David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, USA.; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA., Elledge SJ; Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA. selledge@genetics.med.harvard.edu.; Department of Genetics, Harvard Medical School, Boston, MA, USA. selledge@genetics.med.harvard.edu.; Howard Hughes Medical Institute, Chevy Chase, MD, USA. selledge@genetics.med.harvard.edu.
المصدر: Nature communications [Nat Commun] 2022 Jan 11; Vol. 13 (1), pp. 256. Date of Electronic Publication: 2022 Jan 11.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.
اللغة: English
بيانات الدورية: Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE
أسماء مطبوعة: Original Publication: [London] : Nature Pub. Group
مواضيع طبية MeSH: Biological Transport/*physiology , GATA4 Transcription Factor/*metabolism , Neoplasms/*metabolism , T-Lymphocytes, Cytotoxic/*metabolism, Animals ; Antibodies, Monoclonal, Humanized ; Chemokine CCL2/metabolism ; GATA4 Transcription Factor/genetics ; Gene Expression Regulation, Neoplastic ; Homeodomain Proteins ; Humans ; Immune Evasion ; Lung/pathology ; Melanoma ; Mice ; Mice, Inbred C57BL ; Myocytes, Cardiac/metabolism ; Neoplasms/immunology ; Neoplasms/pathology ; Transcriptome
مستخلص: The GATA4 transcription factor acts as a master regulator of development of multiple tissues. GATA4 also acts in a distinct capacity to control a stress-inducible pro-inflammatory secretory program that is associated with senescence, a potent tumor suppression mechanism, but also operates in non-senescent contexts such as tumorigenesis. This secretory pathway is composed of chemokines, cytokines, growth factors, and proteases. Since GATA4 is deleted or epigenetically silenced in cancer, here we examine the role of GATA4 in tumorigenesis in mouse models through both loss-of-function and overexpression experiments. We find that GATA4 promotes non-cell autonomous tumor suppression in multiple model systems. Mechanistically, we show that Gata4-dependent tumor suppression requires cytotoxic CD8 T cells and partially requires the secreted chemokine CCL2. Analysis of transcriptome data in human tumors reveals reduced lymphocyte infiltration in GATA4-deficient tumors, consistent with our murine data. Notably, activation of the GATA4-dependent secretory program combined with an anti-PD-1 antibody robustly abrogates tumor growth in vivo.
(© 2022. The Author(s).)
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معلومات مُعتمدة: F31 CA224796 United States CA NCI NIH HHS; P30 CA014051 United States CA NCI NIH HHS; R01 CA234600 United States CA NCI NIH HHS; United States HHMI Howard Hughes Medical Institute
المشرفين على المادة: 0 (Antibodies, Monoclonal, Humanized)
0 (Chemokine CCL2)
0 (GATA4 Transcription Factor)
0 (GATA4 protein, human)
0 (Gata4 protein, mouse)
0 (Homeodomain Proteins)
128559-51-3 (RAG-1 protein)
52CMI0WC3Y (atezolizumab)
تواريخ الأحداث: Date Created: 20220112 Date Completed: 20220210 Latest Revision: 20221024
رمز التحديث: 20221213
مُعرف محوري في PubMed: PMC8752777
DOI: 10.1038/s41467-021-27731-5
PMID: 35017504
قاعدة البيانات: MEDLINE
الوصف
تدمد:2041-1723
DOI:10.1038/s41467-021-27731-5