دورية أكاديمية
أعرض في EDS

Hypoxia-inducible factor activity promotes antitumor effector function and tissue residency by CD8+ T cells.

التفاصيل البيبلوغرافية
العنوان: Hypoxia-inducible factor activity promotes antitumor effector function and tissue residency by CD8+ T cells.
المؤلفون: Liikanen I; Division of Biological Sciences, Section of Molecular Biology, University of California San Diego, San Diego, California, USA., Lauhan C; Division of Biological Sciences, Section of Molecular Biology, University of California San Diego, San Diego, California, USA., Quon S; Division of Biological Sciences, Section of Molecular Biology, University of California San Diego, San Diego, California, USA., Omilusik K; Division of Biological Sciences, Section of Molecular Biology, University of California San Diego, San Diego, California, USA., Phan AT; Division of Biological Sciences, Section of Molecular Biology, University of California San Diego, San Diego, California, USA., Bartrolí LB; Division of Biological Sciences, Section of Molecular Biology, University of California San Diego, San Diego, California, USA., Ferry A; Division of Biological Sciences, Section of Molecular Biology, University of California San Diego, San Diego, California, USA., Goulding J; Division of Biological Sciences, Section of Molecular Biology, University of California San Diego, San Diego, California, USA., Chen J; Division of Signaling and Gene Expression, La Jolla Institute for Immunology, La Jolla, California, USA., Scott-Browne JP; Division of Signaling and Gene Expression, La Jolla Institute for Immunology, La Jolla, California, USA., Yustein JT; Texas Children's Cancer and Hematology Centers and The Faris D. Virani Ewing Sarcoma Center, Baylor College of Medicine, Houston, Texas, USA., Scharping NE; Division of Biological Sciences, Section of Molecular Biology, University of California San Diego, San Diego, California, USA., Witherden DA; Division of Biological Sciences, Section of Molecular Biology, University of California San Diego, San Diego, California, USA., Goldrath AW; Division of Biological Sciences, Section of Molecular Biology, University of California San Diego, San Diego, California, USA.
المصدر: The Journal of clinical investigation [J Clin Invest] 2021 Apr 01; Vol. 131 (7).
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: American Society for Clinical Investigation Country of Publication: United States NLM ID: 7802877 Publication Model: Print Cited Medium: Internet ISSN: 1558-8238 (Electronic) Linking ISSN: 00219738 NLM ISO Abbreviation: J Clin Invest Subsets: MEDLINE
أسماء مطبوعة: Publication: 1999- : Ann Arbor, MI : American Society for Clinical Investigation
Original Publication: New Haven [etc.] American Society for Clinical Investigation.
مواضيع طبية MeSH: Immunity, Cellular* , Immunologic Memory*, Basic Helix-Loop-Helix Transcription Factors/*immunology , CD8-Positive T-Lymphocytes/*immunology , Hypoxia-Inducible Factor 1, alpha Subunit/*immunology , Lymphocytes, Tumor-Infiltrating/*immunology , Neoplasms, Experimental/*immunology, Animals ; Basic Helix-Loop-Helix Transcription Factors/genetics ; CD8-Positive T-Lymphocytes/pathology ; Cell Line, Tumor ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics ; Lymphocytes, Tumor-Infiltrating/pathology ; Mice ; Mice, Knockout ; Neoplasms, Experimental/genetics ; Neoplasms, Experimental/pathology ; Von Hippel-Lindau Tumor Suppressor Protein/genetics ; Von Hippel-Lindau Tumor Suppressor Protein/immunology
مستخلص: Adoptive T cell therapies (ACTs) hold great promise in cancer treatment, but low overall response rates in patients with solid tumors underscore remaining challenges in realizing the potential of this cellular immunotherapy approach. Promoting CD8+ T cell adaptation to tissue residency represents an underutilized but promising strategy to improve tumor-infiltrating lymphocyte (TIL) function. Here, we report that deletion of the HIF negative regulator von Hippel-Lindau (VHL) in CD8+ T cells induced HIF-1α/HIF-2α-dependent differentiation of tissue-resident memory-like (Trm-like) TILs in mouse models of malignancy. VHL-deficient TILs accumulated in tumors and exhibited a core Trm signature despite an exhaustion-associated phenotype, which led to retained polyfunctionality and response to αPD-1 immunotherapy, resulting in tumor eradication and protective tissue-resident memory. VHL deficiency similarly facilitated enhanced accumulation of chimeric antigen receptor (CAR) T cells with a Trm-like phenotype in tumors. Thus, HIF activity in CD8+ TILs promotes accumulation and antitumor activity, providing a new strategy to enhance the efficacy of ACTs.
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معلومات مُعتمدة: R01 AI067545 United States AI NIAID NIH HHS; R01 AI040127 United States AI NIAID NIH HHS; T32 GM133351 United States GM NIGMS NIH HHS; R01 AI109842 United States AI NIAID NIH HHS; U19 AI109976 United States AI NIAID NIH HHS; R56 AI109842 United States AI NIAID NIH HHS; R37 AI067545 United States AI NIAID NIH HHS; T32 GM007240 United States GM NIGMS NIH HHS; K00 CA222711 United States CA NCI NIH HHS
فهرسة مساهمة: Keywords: Adaptive immunity; Immunology; Immunotherapy; T cells; Therapeutics
المشرفين على المادة: 0 (Basic Helix-Loop-Helix Transcription Factors)
0 (Hif1a protein, mouse)
0 (Hypoxia-Inducible Factor 1, alpha Subunit)
1B37H0967P (endothelial PAS domain-containing protein 1)
EC 2.3.2.27 (Von Hippel-Lindau Tumor Suppressor Protein)
EC 6.3.2.- (VHL protein, mouse)
تواريخ الأحداث: Date Created: 20210401 Date Completed: 20210928 Latest Revision: 20230801
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC8011896
DOI: 10.1172/JCI143729
PMID: 33792560
قاعدة البيانات: MEDLINE
الوصف
تدمد:1558-8238
DOI:10.1172/JCI143729