دورية أكاديمية
أعرض في EDS

T antigen-specific CD8+ T cells associate with PD-1 blockade response in virus-positive Merkel cell carcinoma.

التفاصيل البيبلوغرافية
العنوان: T antigen-specific CD8+ T cells associate with PD-1 blockade response in virus-positive Merkel cell carcinoma.
المؤلفون: Hansen UK; Section of Experimental and Translational Immunology, Department of Health Technology, Technical University of Denmark, Kongens Lyngby, Denmark.; PokeAcell Aps, BioInnovation Institute, Copenhagen, Denmark., Church CD; Department of Dermatology, Department of Medicine, University of Washington, Seattle, Washington, USA., Carnaz Simões AM; PokeAcell Aps, BioInnovation Institute, Copenhagen, Denmark., Frej MS; Section of Experimental and Translational Immunology, Department of Health Technology, Technical University of Denmark, Kongens Lyngby, Denmark.; PokeAcell Aps, BioInnovation Institute, Copenhagen, Denmark., Bentzen AK; Section of Experimental and Translational Immunology, Department of Health Technology, Technical University of Denmark, Kongens Lyngby, Denmark., Tvingsholm SA; Section of Experimental and Translational Immunology, Department of Health Technology, Technical University of Denmark, Kongens Lyngby, Denmark., Becker JC; Department of Translational Skin Cancer Research, University Hospital Essen and German Cancer Consortium (DKTK), Essen, Germany.; German Cancer Research Center (DKFZ), Heidelberg, Germany.; Department of Dermatology, University Hospital Essen, Essen, Germany., Fling SP; Fred Hutchinson Cancer Center, Seattle, Washington, USA., Ramchurren N; Fred Hutchinson Cancer Center, Seattle, Washington, USA., Topalian SL; Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.; Bloomberg-Kimmel Institute for Cancer Immunotherapy, Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland, USA., Nghiem PT; Department of Dermatology, Department of Medicine, University of Washington, Seattle, Washington, USA.; Fred Hutchinson Cancer Center, Seattle, Washington, USA., Hadrup SR; Section of Experimental and Translational Immunology, Department of Health Technology, Technical University of Denmark, Kongens Lyngby, Denmark.
المصدر: The Journal of clinical investigation [J Clin Invest] 2024 Jan 30; Vol. 134 (8). Date of Electronic Publication: 2024 Jan 30.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: American Society for Clinical Investigation Country of Publication: United States NLM ID: 7802877 Publication Model: Electronic 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: Carcinoma, Merkel Cell*/drug therapy , Carcinoma, Merkel Cell*/genetics , Skin Neoplasms*/drug therapy , Skin Neoplasms*/genetics, Humans ; Antigens, Viral, Tumor ; Programmed Cell Death 1 Receptor/genetics ; CD8-Positive T-Lymphocytes
مستخلص: Merkel cell carcinoma (MCC) is a highly immunogenic skin cancer primarily induced by Merkel cell polyomavirus, which is driven by the expression of the oncogenic T antigens (T-Ags). Blockade of the programmed cell death protein-1 (PD-1) pathway has shown remarkable response rates, but evidence for therapy-associated T-Ag-specific immune response and therapeutic strategies for the nonresponding fraction are both limited. We tracked T-Ag-reactive CD8+ T cells in peripheral blood of 26 MCC patients under anti-PD1 therapy, using DNA-barcoded pMHC multimers, displaying all peptides from the predicted HLA ligandome of the oncoproteins, covering 33 class I haplotypes. We observed a broad T cell recognition of T-Ags, including identification of 20 T-Ag-derived epitopes we believe to be novel. Broadening of the T-Ag recognition profile and increased T cell frequencies during therapy were strongly associated with clinical response and prolonged progression-free survival. T-Ag-specific T cells could be further boosted and expanded directly from peripheral blood using artificial antigen-presenting scaffolds, even in patients with no detectable T-Ag-specific T cells. These T cells provided strong tumor-rejection capacity while retaining a favorable phenotype for adoptive cell transfer. These findings demonstrate that T-Ag-specific T cells are associated with the clinical outcome to PD-1 blockade and that Ag-presenting scaffolds can be used to boost such responses.
References: JAMA Oncol. 2018 Sep 1;4(9):e180077. (PMID: 29566106)
Nat Med. 2019 Aug;25(8):1251-1259. (PMID: 31359002)
Cancer Immunol Res. 2020 May;8(5):648-659. (PMID: 32179557)
Nat Cancer. 2020 Feb;1(2):210-221. (PMID: 32110781)
Sci Immunol. 2019 Jul 19;4(37):. (PMID: 31324690)
Science. 2008 Feb 22;319(5866):1096-100. (PMID: 18202256)
Nat Med. 2006 Feb;12(2):246-51. (PMID: 16462803)
Cancer Immunol Immunother. 2019 Jun;68(6):983-990. (PMID: 30993371)
Cancer Immunol Res. 2014 Jan;2(1):27-36. (PMID: 24432305)
J Immunother Cancer. 2023 Aug;11(8):. (PMID: 37586765)
N Engl J Med. 2022 Dec 8;387(23):2113-2125. (PMID: 36477031)
Nature. 2019 Oct;574(7780):696-701. (PMID: 31645760)
Nat Rev Clin Oncol. 2018 Dec;15(12):763-776. (PMID: 30287935)
J Immunother Cancer. 2022 Sep;10(9):. (PMID: 36252564)
Cell. 2020 Jun 25;181(7):1612-1625.e13. (PMID: 32497499)
J Invest Dermatol. 2022 Jan;142(1):239-243.e13. (PMID: 34298058)
Nature. 2018 May;557(7706):575-579. (PMID: 29769722)
J Virol. 2010 Jul;84(14):7064-72. (PMID: 20444890)
Clin Cancer Res. 2019 Apr 1;25(7):2144-2154. (PMID: 30647082)
Clin Cancer Res. 2014 Apr 1;20(7):1768-78. (PMID: 24526738)
Eur J Cancer. 2009 Jan;45(2):228-47. (PMID: 19097774)
Science. 2015 Apr 3;348(6230):124-8. (PMID: 25765070)
Am J Clin Pathol. 2014 Oct;142(4):452-8. (PMID: 25239411)
Nat Protoc. 2006;1(3):1120-32. (PMID: 17406393)
Methods Mol Biol. 2009;524:383-405. (PMID: 19377960)
Cancer. 2017 Apr 15;123(8):1464-1474. (PMID: 27925665)
Cancer Immunol Res. 2019 Oct;7(10):1727-1739. (PMID: 31405946)
Nat Commun. 2018 Jul 13;9(1):2724. (PMID: 30006565)
Proc Natl Acad Sci U S A. 2008 Mar 11;105(10):3825-30. (PMID: 18308940)
J Invest Dermatol. 2013 Mar;133(3):642-646. (PMID: 23190897)
Cancer Cell. 2019 Sep 16;36(3):215-217. (PMID: 31526757)
Nat Protoc. 2012 Apr 12;7(5):891-902. (PMID: 22498709)
Oncotarget. 2016 Jan 19;7(3):3403-15. (PMID: 26655088)
J Immunother Cancer. 2021 Apr;9(4):. (PMID: 33879601)
Nat Med. 2019 Mar;25(3):454-461. (PMID: 30804515)
J Immunother Cancer. 2023 Aug;11(8):. (PMID: 37536935)
Oncoimmunology. 2012 Nov 1;1(8):1420-1421. (PMID: 23243614)
Nat Commun. 2018 Sep 24;9(1):3868. (PMID: 30250229)
Nature. 2017 May 4;545(7652):60-65. (PMID: 28397821)
J Immunol. 2017 Nov 1;199(9):3360-3368. (PMID: 28978689)
J Clin Invest. 2022 Jul 1;132(13):. (PMID: 35775490)
Cancer Res. 2018 Jan 1;78(1):115-128. (PMID: 29066514)
Nat Biotechnol. 2016 Oct;34(10):1037-1045. (PMID: 27571370)
J Clin Oncol. 2020 Aug 1;38(22):2476-2487. (PMID: 32324435)
Eur J Dermatol. 2021 Jun 1;31(3):381-391. (PMID: 34080974)
Nat Commun. 2022 Apr 11;13(1):1935. (PMID: 35410325)
Nat Rev Immunol. 2018 Oct;18(10):635-647. (PMID: 30057419)
Proc Natl Acad Sci U S A. 2017 May 9;114(19):4993-4998. (PMID: 28446615)
J Am Acad Dermatol. 2022 Jun;86(6):1385-1387. (PMID: 34082038)
Cancer Immunol Res. 2020 Mar;8(3):334-344. (PMID: 31871122)
Cancer Immunol Res. 2017 Feb;5(2):137-147. (PMID: 28093446)
معلومات مُعتمدة: P01 CA225517 United States CA NCI NIH HHS; P30 CA015704 United States CA NCI NIH HHS
فهرسة مساهمة: Keywords: Cancer immunotherapy; Immunology; Oncology; Skin cancer; T cells
المشرفين على المادة: 0 (Antigens, Viral, Tumor)
0 (Programmed Cell Death 1 Receptor)
تواريخ الأحداث: Date Created: 20240415 Date Completed: 20240416 Latest Revision: 20240420
رمز التحديث: 20240420
مُعرف محوري في PubMed: PMC11014655
DOI: 10.1172/JCI177082
PMID: 38618958
قاعدة البيانات: MEDLINE
الوصف
تدمد:1558-8238
DOI:10.1172/JCI177082