دورية أكاديمية
أعرض في EDS

Single cell analysis reveals distinct immune landscapes in transplant and primary sarcomas that determine response or resistance to immunotherapy.

التفاصيل البيبلوغرافية
العنوان: Single cell analysis reveals distinct immune landscapes in transplant and primary sarcomas that determine response or resistance to immunotherapy.
المؤلفون: Wisdom AJ; Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC, 27708, USA., Mowery YM; Department of Radiation Oncology, Duke University Medical Center, Durham, NC, 27708, USA. yvonne.mowery@duke.edu.; Duke Cancer Institute, Durham, NC, 27708, USA. yvonne.mowery@duke.edu., Hong CS; Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC, 27708, USA., Himes JE; Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC, 27708, USA., Nabet BY; Stanford Cancer Institute, Stanford University, Stanford, CA, 94305, USA.; Department of Oncology Biomarker Development, Genentech, South San Francisco, CA, 94080, USA., Qin X; Duke Cancer Institute, Durham, NC, 27708, USA., Zhang D; Duke Cancer Institute, Durham, NC, 27708, USA., Chen L; Merck & Co., Inc, Kenilworth, NJ, 07033, USA., Fradin H; Duke Center for Genomic and Computational Biology, Durham, NC, 27708, USA., Patel R; Department of Radiation Oncology, Duke University Medical Center, Durham, NC, 27708, USA., Bassil AM; Department of Radiation Oncology, Duke University Medical Center, Durham, NC, 27708, USA., Muise ES; Merck & Co., Inc, Kenilworth, NJ, 07033, USA., King DA; Stanford Cancer Institute, Stanford University, Stanford, CA, 94305, USA.; Division of Oncology, Department of Medicine, Stanford University, Stanford, CA, 94305, USA., Xu ES; Department of Radiation Oncology, Duke University Medical Center, Durham, NC, 27708, USA., Carpenter DJ; Department of Radiation Oncology, Duke University Medical Center, Durham, NC, 27708, USA., Kent CL; Department of Radiation Oncology, Duke University Medical Center, Durham, NC, 27708, USA., Smythe KS; Fred Hutchinson Cancer Research Center, Seattle, WA, 98109, USA., Williams NT; Department of Radiation Oncology, Duke University Medical Center, Durham, NC, 27708, USA., Luo L; Department of Radiation Oncology, Duke University Medical Center, Durham, NC, 27708, USA., Ma Y; Department of Radiation Oncology, Duke University Medical Center, Durham, NC, 27708, USA., Alizadeh AA; Stanford Cancer Institute, Stanford University, Stanford, CA, 94305, USA.; Division of Oncology, Department of Medicine, Stanford University, Stanford, CA, 94305, USA.; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, CA, 94305, USA., Owzar K; Duke Cancer Institute, Durham, NC, 27708, USA.; Department of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, NC, 27710, USA., Diehn M; Stanford Cancer Institute, Stanford University, Stanford, CA, 94305, USA.; Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, Stanford, CA, 94305, USA.; Department of Radiation Oncology, Stanford University, Stanford, CA, 94305, USA., Bradley T; Department of Medicine, Duke University Medical Center, Durham, NC, 27710, USA.; Center for Pediatric Genomic Medicine, Children's Mercy Kansas City, Kansas City, MO, 64108, USA., Kirsch DG; Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC, 27708, USA. david.kirsch@duke.edu.; Department of Radiation Oncology, Duke University Medical Center, Durham, NC, 27708, USA. david.kirsch@duke.edu.; Duke Cancer Institute, Durham, NC, 27708, USA. david.kirsch@duke.edu.
المصدر: Nature communications [Nat Commun] 2020 Dec 17; Vol. 11 (1), pp. 6410. Date of Electronic Publication: 2020 Dec 17.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
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: Sarcoma/*therapy , Single-Cell Analysis/*methods , Tumor Microenvironment/*immunology, Animals ; Antineoplastic Agents, Immunological/pharmacology ; Bone Marrow Transplantation ; CD8-Positive T-Lymphocytes/immunology ; DNA-Binding Proteins/genetics ; Drug Resistance, Neoplasm/immunology ; Gene Expression Regulation, Neoplastic ; Humans ; Immunotherapy ; Mice, Inbred Strains ; Programmed Cell Death 1 Receptor/antagonists & inhibitors ; Sarcoma/genetics ; Sarcoma/immunology ; Tumor Escape ; Tumor Microenvironment/genetics ; Exome Sequencing
مستخلص: Immunotherapy fails to cure most cancer patients. Preclinical studies indicate that radiotherapy synergizes with immunotherapy, promoting radiation-induced antitumor immunity. Most preclinical immunotherapy studies utilize transplant tumor models, which overestimate patient responses. Here, we show that transplant sarcomas are cured by PD-1 blockade and radiotherapy, but identical treatment fails in autochthonous sarcomas, which demonstrate immunoediting, decreased neoantigen expression, and tumor-specific immune tolerance. We characterize tumor-infiltrating immune cells from transplant and primary tumors, revealing striking differences in their immune landscapes. Although radiotherapy remodels myeloid cells in both models, only transplant tumors are enriched for activated CD8+ T cells. The immune microenvironment of primary murine sarcomas resembles most human sarcomas, while transplant sarcomas resemble the most inflamed human sarcomas. These results identify distinct microenvironments in murine sarcomas that coevolve with the immune system and suggest that patients with a sarcoma immune phenotype similar to transplant tumors may benefit most from PD-1 blockade and radiotherapy.
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معلومات مُعتمدة: R38 CA245204 United States CA NCI NIH HHS; U24 CA220245 United States CA NCI NIH HHS; P30 CA016086 United States CA NCI NIH HHS; U54 CA168512 United States CA NCI NIH HHS; R01 CA233975 United States CA NCI NIH HHS; P01 CA142538 United States CA NCI NIH HHS; T32 GM007171 United States GM NIGMS NIH HHS; F30 CA221268 United States CA NCI NIH HHS; R35 CA197616 United States CA NCI NIH HHS; P30 CA014236 United States CA NCI NIH HHS; T32 GM145449 United States GM NIGMS NIH HHS
سلسلة جزيئية: figshare 10.6084/m9.figshare.5821263.v3
المشرفين على المادة: 0 (Antineoplastic Agents, Immunological)
0 (DNA-Binding Proteins)
0 (Pdcd1 protein, mouse)
0 (Programmed Cell Death 1 Receptor)
0 (Rag2 protein, mouse)
تواريخ الأحداث: Date Created: 20201218 Date Completed: 20210112 Latest Revision: 20240501
رمز التحديث: 20240501
مُعرف محوري في PubMed: PMC7746723
DOI: 10.1038/s41467-020-19917-0
PMID: 33335088
قاعدة البيانات: MEDLINE
الوصف
تدمد:2041-1723
DOI:10.1038/s41467-020-19917-0