دورية أكاديمية
Senescent CAFs Mediate Immunosuppression and Drive Breast Cancer Progression.
| العنوان: | Senescent CAFs Mediate Immunosuppression and Drive Breast Cancer Progression. |
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| المؤلفون: | Ye J; Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, Missouri., Baer JM; Department of Medicine, Washington University School of Medicine, St. Louis, Missouri., Faget DV; Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, Missouri., Morikis VA; Department of Medicine, Washington University School of Medicine, St. Louis, Missouri., Ren Q; Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, Missouri., Melam A; Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, Missouri., Delgado AP; Graduate Program in Genetics, Stony Brook University, Stony Brook, New York., Luo X; Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, Missouri., Bagchi SM; Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, Missouri., Belle JI; Department of Medicine, Washington University School of Medicine, St. Louis, Missouri., Campos E; Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, Missouri.; Medical Scientist Training Program, Washington University School of Medicine, St. Louis, Missouri., Friedman M; Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, Missouri., Veis DJ; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri., Knudsen ES; Department of Molecular and Cellular Biology, Roswell Park Comprehensive Cancer Center, Buffalo, New York., Witkiewicz AK; Department of Molecular and Cellular Biology, Roswell Park Comprehensive Cancer Center, Buffalo, New York., Powers S; Department of Pathology and Cancer Center, Renaissance School of Medicine, Stony Brook, New York., Longmore GD; Department of Medicine, Washington University School of Medicine, St. Louis, Missouri.; ICCE Institute, Washington University School of Medicine, St. Louis, Missouri.; Siteman Cancer Center, Washington University School of Medicine, St. Louis, Missouri., DeNardo DG; Department of Medicine, Washington University School of Medicine, St. Louis, Missouri.; ICCE Institute, Washington University School of Medicine, St. Louis, Missouri.; Siteman Cancer Center, Washington University School of Medicine, St. Louis, Missouri., Stewart SA; Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, Missouri.; Department of Medicine, Washington University School of Medicine, St. Louis, Missouri.; ICCE Institute, Washington University School of Medicine, St. Louis, Missouri.; Siteman Cancer Center, Washington University School of Medicine, St. Louis, Missouri. |
| المصدر: | Cancer discovery [Cancer Discov] 2024 Jul 01; Vol. 14 (7), pp. 1302-1323. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Association for Cancer Research Country of Publication: United States NLM ID: 101561693 Publication Model: Print Cited Medium: Internet ISSN: 2159-8290 (Electronic) Linking ISSN: 21598274 NLM ISO Abbreviation: Cancer Discov Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Philadelphia, PA : American Association for Cancer Research |
| مواضيع طبية MeSH: | Breast Neoplasms*/immunology , Breast Neoplasms*/pathology , Breast Neoplasms*/genetics , Disease Progression* , Cancer-Associated Fibroblasts*/metabolism , Cancer-Associated Fibroblasts*/immunology , Tumor Microenvironment*/immunology, Animals ; Female ; Mice ; Humans ; Killer Cells, Natural/immunology ; Cellular Senescence/immunology |
| مستخلص: | The tumor microenvironment (TME) profoundly influences tumorigenesis, with gene expression in the breast TME capable of predicting clinical outcomes. The TME is complex and includes distinct cancer-associated fibroblast (CAF) subtypes whose contribution to tumorigenesis remains unclear. Here, we identify a subset of myofibroblast CAFs (myCAF) that are senescent (senCAF) in mouse and human breast tumors. Utilizing the MMTV-PyMT;INK-ATTAC (INK) mouse model, we found that senCAF-secreted extracellular matrix specifically limits natural killer (NK) cell cytotoxicity to promote tumor growth. Genetic or pharmacologic senCAF elimination unleashes NK cell killing, restricting tumor growth. Finally, we show that senCAFs are present in HER2+, ER+, and triple-negative breast cancer and in ductal carcinoma in situ (DCIS) where they predict tumor recurrence. Together, these findings demonstrate that senCAFs are potently tumor promoting and raise the possibility that targeting them by senolytic therapy could restrain breast cancer development. Significance: senCAFs limit NK cell-mediated killing, thereby contributing to breast cancer progression. Thus, targeting senCAFs could be a clinically viable approach to limit tumor progression. See related article by Belle et al., p. 1324. (©2024 American Association for Cancer Research.) |
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| معلومات مُعتمدة: | CA223758 Center for Cancer Research (CCR); R01 CA217208 United States CA NCI NIH HHS; U01 CA284086 United States CA NCI NIH HHS; U54 AG075934 United States AG NIA NIH HHS; R01 CA262555 United States CA NCI NIH HHS; CA217208 Center for Cancer Research (CCR); P50 CA272213 United States CA NCI NIH HHS; GM7200-49 National Institute of General Medical Sciences (NIGMS); R01 CA244938 United States CA NCI NIH HHS; CA113275 Center for Cancer Research (CCR); CA275212 Center for Cancer Research (CCR); DK122633 Division of Diabetes, Endocrinology, and Metabolic Diseases (DEM); BC181712 U.S. Department of Defense (DOD); CA21720605 Center for Cancer Research (CCR); AG059244 National Institute on Aging (NIA); R01 CA262506 United States CA NCI NIH HHS; P30CA091842 Center for Cancer Research (CCR); R01 CA248917 United States CA NCI NIH HHS; R01 CA177670 United States CA NCI NIH HHS; CA271721 Center for Cancer Research (CCR); CA254060 Center for Cancer Research (CCR); R01 AG059244 United States AG NIA NIH HHS |
| تواريخ الأحداث: | Date Created: 20240429 Date Completed: 20240701 Latest Revision: 20240703 |
| رمز التحديث: | 20240703 |
| مُعرف محوري في PubMed: | PMC11216870 |
| DOI: | 10.1158/2159-8290.CD-23-0426 |
| PMID: | 38683161 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 2159-8290 |
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| DOI: | 10.1158/2159-8290.CD-23-0426 |