{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T05:58:57Z","timestamp":1790834337993,"version":"4.1.0"},"reference-count":56,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2020,3,10]],"date-time":"2020-03-10T00:00:00Z","timestamp":1583798400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001102","name":"Cancer Council NSW","doi-asserted-by":"publisher","award":["18-05"],"award-info":[{"award-number":["18-05"]}],"id":[{"id":"10.13039\/501100001102","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001102","name":"Cancer Council NSW","doi-asserted-by":"publisher","award":["APP1147639 RG18\/12"],"award-info":[{"award-number":["APP1147639 RG18\/12"]}],"id":[{"id":"10.13039\/501100001102","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["APP1093017"],"award-info":[{"award-number":["APP1093017"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["GNT1037298"],"award-info":[{"award-number":["GNT1037298"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"DOI":"10.3389\/fimmu.2020.00372","type":"journal-article","created":{"date-parts":[[2020,3,10]],"date-time":"2020-03-10T06:02:41Z","timestamp":1583820161000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":34,"title":["Pretreatment Innate Cell Populations and CD4 T Cells in Blood Are Associated With Response to Immune Checkpoint Blockade in Melanoma Patients"],"prefix":"10.3389","volume":"11","author":[{"given":"Mehdi R.","family":"Pirozyan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen M.","family":"McGuire","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdullah Al","family":"Emran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsin-Yi","family":"Tseng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessamy C.","family":"Tiffen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenny H.","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo S.","family":"Carlino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander M.","family":"Menzies","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgina V.","family":"Long","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard A.","family":"Scolyer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Fazekas de St Groth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Hersey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2020,3,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"165","DOI":"10.2217\/mmt.14.14","article-title":"How anti-PD1 treatments are changing the management of melanoma","volume":"1","author":"Hersey","year":"2014","journal-title":"Melanoma Manag."},{"key":"B2","doi-asserted-by":"publisher","first-page":"450","DOI":"10.1016\/j.ccell.2015.03.001","article-title":"Immune checkpoint blockade: a common denominator approach to cancer therapy","volume":"27","author":"Topalian","year":"2015","journal-title":"Cancer Cell."},{"key":"B3","doi-asserted-by":"publisher","first-page":"2521","DOI":"10.1056\/NEJMoa1503093","article-title":"Pembrolizumab versus ipilimumab in advanced melanoma","volume":"372","author":"Robert","year":"2015","journal-title":"N Engl J Med."},{"key":"B4","doi-asserted-by":"publisher","first-page":"1600","DOI":"10.1001\/jama.2016.4059","article-title":"Association of pembrolizumab with tumor response and survival among patients with advanced melanoma","volume":"315","author":"Ribas","year":"2016","journal-title":"JAMA."},{"key":"B5","doi-asserted-by":"publisher","first-page":"707","DOI":"10.1016\/j.cell.2017.01.017","article-title":"Primary, adaptive, and acquired resistance to cancer immunotherapy","volume":"168","author":"Sharma","year":"2017","journal-title":"Cell."},{"key":"B6","doi-asserted-by":"publisher","first-page":"1350","DOI":"10.1126\/science.aar4060","article-title":"Cancer immunotherapy using checkpoint blockade","volume":"359","author":"Ribas","year":"2018","journal-title":"Science."},{"key":"B7","doi-asserted-by":"publisher","first-page":"4102","DOI":"10.1200\/JCO.2016.67.2477","article-title":"Programmed death-ligand 1 expression and response to the anti-programmed death 1 antibody pembrolizumab in melanoma","volume":"34","author":"Daud","year":"2016","journal-title":"J Clin Oncol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"5064","DOI":"10.1158\/1078-0432.CCR-13-3271","article-title":"Association of PD-1, PD-1 ligands, and other features of the tumor immune microenvironment with response to anti-PD-1 therapy","volume":"20","author":"Taube","year":"2014","journal-title":"Clin Cancer Res."},{"key":"B9","doi-asserted-by":"publisher","first-page":"3915","DOI":"10.1158\/1078-0432.CCR-15-1714","article-title":"PD-L1 negative status is associated with lower mutation burden, differential expression of immune-related genes, and worse survival in stage III melanoma","volume":"22","author":"Madore","year":"2016","journal-title":"Clin Cancer Res."},{"key":"B10","doi-asserted-by":"publisher","first-page":"1480","DOI":"10.1016\/S1470-2045(18)30700-9","article-title":"Nivolumab plus ipilimumab or nivolumab alone versus ipilimumab alone in advanced melanoma (CheckMate 067): 4-year outcomes of a multicentre, randomised, phase 3 trial","volume":"19","author":"Hodi","year":"2018","journal-title":"Lancet Oncol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"818","DOI":"10.1158\/2159-8290.CD-16-0694","article-title":"Checkpoint immunotherapy: picking a winner","volume":"6","author":"Teng","year":"2016","journal-title":"Cancer Discov."},{"key":"B12","doi-asserted-by":"publisher","first-page":"1136","DOI":"10.1038\/s41467-017-01062-w","article-title":"Resistance to checkpoint blockade therapy through inactivation of antigen presentation","volume":"8","author":"Sade-Feldman","year":"2017","journal-title":"Nat Commun."},{"key":"B13","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1016\/j.cell.2014.12.033","article-title":"Molecular and genetic properties of tumors associated with local immune cytolytic activity","volume":"160","author":"Rooney","year":"2015","journal-title":"Cell."},{"key":"B14","doi-asserted-by":"publisher","first-page":"537","DOI":"10.1038\/nature23477","article-title":"Identification of essential genes for cancer immunotherapy","volume":"548","author":"Patel","year":"2017","journal-title":"Nature."},{"key":"B15","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1038\/nature23270","article-title":"In vivo CRISPR screening identifies Ptpn2 as a cancer immunotherapy target","volume":"547","author":"Manguso","year":"2017","journal-title":"Nature."},{"key":"B16","doi-asserted-by":"publisher","first-page":"984","DOI":"10.1016\/j.cell.2018.09.006","article-title":"A cancer cell program promotes T cell exclusion and resistance to checkpoint blockade","volume":"175","author":"Jerby-Arnon","year":"2018","journal-title":"Cell."},{"key":"B17","doi-asserted-by":"publisher","first-page":"1271","DOI":"10.1016\/j.cell.2015.07.061","article-title":"Non-genomic and immune evolution of melanoma acquiring MAPKi resistance","volume":"162","author":"Hugo","year":"2015","journal-title":"Cell."},{"key":"B18","doi-asserted-by":"publisher","first-page":"486","DOI":"10.1038\/nri3862","article-title":"Molecular and cellular insights into T cell exhaustion","volume":"15","author":"Wherry","year":"2015","journal-title":"Nat Rev Immunol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"190","DOI":"10.1038\/nature21508","article-title":"Immunology: the chronicles of T-cell exhaustion","volume":"543","author":"Amezquita","year":"2017","journal-title":"Nature."},{"key":"B20","doi-asserted-by":"publisher","first-page":"1165","DOI":"10.1126\/science.aae0491","article-title":"The epigenetic landscape of T cell exhaustion","volume":"354","author":"Sen","year":"2016","journal-title":"Science."},{"key":"B21","doi-asserted-by":"publisher","first-page":"455","DOI":"10.3389\/fimmu.2013.00455","article-title":"Inhibitory receptor expression depends more dominantly on differentiation and activation than \u201cexhaustion\u201d of human CD8 T cells","volume":"4","author":"Legat","year":"2013","journal-title":"Front Immunol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"1160","DOI":"10.1126\/science.aaf2807","article-title":"Epigenetic stability of exhausted T cells limits durability of reinvigoration by PD-1 blockade","volume":"354","author":"Pauken","year":"2016","journal-title":"Science."},{"key":"B23","doi-asserted-by":"publisher","first-page":"452","DOI":"10.1038\/nature22367","article-title":"Chromatin states define tumour-specific T cell dysfunction and reprogramming","volume":"545","author":"Philip","year":"2017","journal-title":"Nature."},{"key":"B24","doi-asserted-by":"publisher","first-page":"326","DOI":"10.1038\/s41590-019-0312-6","article-title":"Subsets of exhausted CD8(+) T cells differentially mediate tumor control and respond to checkpoint blockade","volume":"20","author":"Miller","year":"2019","journal-title":"Nat Immunol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"775","DOI":"10.1016\/j.cell.2018.11.043","article-title":"Dysfunctional CD8 T cells form a proliferative, dynamically regulated compartment within human melanoma","volume":"176","author":"Li","year":"2019","journal-title":"Cell."},{"key":"B26","doi-asserted-by":"publisher","first-page":"998","DOI":"10.1016\/j.cell.2018.10.038","article-title":"Defining T cell states associated with response to checkpoint immunotherapy in melanoma","volume":"175","author":"Sade-Feldman","year":"2018","journal-title":"Cell."},{"key":"B27","doi-asserted-by":"publisher","first-page":"1550","DOI":"10.1038\/s41591-018-0136-1","article-title":"Signatures of T cell dysfunction and exclusion predict cancer immunotherapy response","volume":"24","author":"Jiang","year":"2018","journal-title":"Nat Med."},{"key":"B28","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1038\/nature22079","article-title":"T-cell invigoration to tumour burden ratio associated with anti-PD-1 response","volume":"545","author":"Huang","year":"2017","journal-title":"Nature."},{"key":"B29","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1038\/nm.4466","article-title":"High-dimensional single-cell analysis predicts response to anti-PD-1 immunotherapy","volume":"24","author":"Krieg","year":"2018","journal-title":"Nat Med."},{"key":"B30","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1186\/s40425-018-0328-8","article-title":"Distinct predictive biomarker candidates for response to anti-CTLA-4 and anti-PD-1 immunotherapy in melanoma patients","volume":"6","author":"Subrahmanyam","year":"2018","journal-title":"J Immunother Cancer."},{"key":"B31","doi-asserted-by":"publisher","first-page":"927","DOI":"10.4049\/jimmunol.1600875","article-title":"Establishing high dimensional immune signatures from peripheral blood via mass cytometry in a discovery cohort of stage IV melanoma patients","volume":"198","author":"Wistuba-Hamprecht","year":"2017","journal-title":"J Immunol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"ix29","DOI":"10.1093\/annonc\/mdm290","article-title":"Response evaluation: beyond RECIST","volume":"18","author":"Eisenhauer","year":"2007","journal-title":"Ann Oncol."},{"key":"B33","doi-asserted-by":"publisher","first-page":"1871","DOI":"10.4049\/jimmunol.1801368","article-title":"High-dimensional mass cytometric analysis reveals an increase in effector regulatory T cells as a distinguishing feature of colorectal tumors","volume":"202","author":"Norton","year":"2019","journal-title":"J Immunol."},{"key":"B34","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1016\/j.immuni.2018.12.021","article-title":"Intratumoral Tcf1(+)PD-1(+)CD8(+) T cells with stem-like properties promote tumor control in response to vaccination and checkpoint blockade immunotherapy","volume":"50","author":"Siddiqui","year":"2019","journal-title":"Immunity."},{"key":"B35","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1038\/s41586-019-1324-y","article-title":"TOX is a critical regulator of tumour-specific T cell differentiation","volume":"571","author":"Scott","year":"2019","journal-title":"Nature."},{"key":"B36","doi-asserted-by":"publisher","first-page":"2797","DOI":"10.1002\/eji.201343751","article-title":"The who's who of T-cell differentiation: human memory T-cell subsets","volume":"43","author":"Mahnke","year":"2013","journal-title":"Eur J Immunol."},{"key":"B37","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1016\/j.it.2017.02.003","article-title":"Transcription factor T-bet orchestrates lineage development and function in the immune system","volume":"38","author":"Kallies","year":"2017","journal-title":"Trends Immunol."},{"key":"B38","doi-asserted-by":"publisher","first-page":"1041","DOI":"10.1126\/science.1090148","article-title":"Control of effector CD8+ T cell function by the transcription factor Eomesodermin","volume":"302","author":"Pearce","year":"2003","journal-title":"Science."},{"key":"B39","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1038\/sj.bjc.6602702","article-title":"Elevated neutrophil and monocyte counts in peripheral blood are associated with poor survival in patients with metastatic melanoma: a prognostic model","volume":"93","author":"Schmidt","year":"2005","journal-title":"Br J Cancer."},{"key":"B40","doi-asserted-by":"publisher","first-page":"596","DOI":"10.1097\/CMR.0000000000000404","article-title":"Lymphocyte-to-monocyte ratio is associated with survival in pembrolizumab-treated metastatic melanoma patients","volume":"27","author":"Failing","year":"2017","journal-title":"Melanoma Res."},{"key":"B41","doi-asserted-by":"publisher","first-page":"1029","DOI":"10.1016\/j.immuni.2018.04.026","article-title":"Epigenomic-guided mass cytometry profiling reveals disease-specific features of exhausted CD8 T cells","volume":"48","author":"Bengsch","year":"2018","journal-title":"Immunity."},{"key":"B42","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1016\/j.immuni.2016.07.021","article-title":"T cell factor 1-expressing memory-like CD8(+) T cells sustain the immune response to chronic viral infections","volume":"45","author":"Utzschneider","year":"2016","journal-title":"Immunity."},{"key":"B43","doi-asserted-by":"publisher","first-page":"1220","DOI":"10.1126\/science.1229620","article-title":"Progenitor and terminal subsets of CD8+ T cells cooperate to contain chronic viral infection","volume":"338","author":"Paley","year":"2012","journal-title":"Science."},{"key":"B44","doi-asserted-by":"publisher","first-page":"238","DOI":"10.1016\/j.ccell.2019.01.003","article-title":"Distinct immune cell populations define response to anti-PD-1 monotherapy and Anti-PD-1\/Anti-CTLA-4 combined therapy","volume":"35","author":"Gide","year":"2019","journal-title":"Cancer Cell."},{"key":"B45","doi-asserted-by":"publisher","first-page":"E2129","DOI":"10.3390\/ijms18102129","article-title":"Control of NK cell activation by immune checkpoint molecules","volume":"18","author":"Beldi-Ferchiou","year":"2017","journal-title":"Int J Mol Sci."},{"key":"B46","doi-asserted-by":"publisher","first-page":"4654","DOI":"10.1172\/JCI99317","article-title":"Contribution of NK cells to immunotherapy mediated by PD-1\/PD-L1 blockade","volume":"128","author":"Hsu","year":"2018","journal-title":"J Clin Invest."},{"key":"B47","doi-asserted-by":"publisher","first-page":"e1537581","DOI":"10.1080\/2162402X.2018.1537581","article-title":"Integrated molecular and immunophenotypic analysis of NK cells in anti-PD-1 treated metastatic melanoma patients","volume":"8","author":"Lee","year":"2019","journal-title":"Oncoimmunology."},{"key":"B48","doi-asserted-by":"publisher","first-page":"4487","DOI":"10.1038\/s41598-019-40933-8","article-title":"Circulating CD56(bright) NK cells inversely correlate with survival of melanoma patients","volume":"9","author":"de Jonge","year":"2019","journal-title":"Sci Rep."},{"key":"B49","doi-asserted-by":"publisher","first-page":"622","DOI":"10.1093\/jnci\/85.8.622","article-title":"Prospective randomized trial of high-dose interleukin-2 alone or in conjunction with lymphokine-activated killer cells for the treatment of patients with advanced cancer","volume":"85","author":"Rosenberg","year":"1993","journal-title":"J Natl Cancer Inst."},{"key":"B50","doi-asserted-by":"publisher","first-page":"14","DOI":"10.3389\/fimmu.2019.00014","article-title":"CD56(dim) CD16(-) natural killer cell profiling in melanoma patients receiving a cancer vaccine and interferon-alpha","volume":"10","author":"Vujanovic","year":"2019","journal-title":"Front Immunol."},{"key":"B51","doi-asserted-by":"publisher","first-page":"301","DOI":"10.3389\/fimmu.2017.00301","article-title":"Immunoregulatory role of NK cells in tissue inflammation and regeneration","volume":"8","author":"Tosello-Trampont","year":"2017","journal-title":"Front Immunol."},{"key":"B52","doi-asserted-by":"publisher","first-page":"599","DOI":"10.1093\/intimm\/dxp029","article-title":"NK cells provide helper signal for CD8+ T cells by inducing the expression of membrane-bound IL-15 on DCs","volume":"21","author":"Morandi","year":"2009","journal-title":"Int Immunol."},{"key":"B53","doi-asserted-by":"publisher","first-page":"5008","DOI":"10.1182\/blood-2007-11-122259","article-title":"A role for interleukin-12\/23 in the maturation of human natural killer and CD56+ T cells in vivo","volume":"111","author":"Guia","year":"2008","journal-title":"Blood."},{"key":"B54","doi-asserted-by":"publisher","first-page":"1698","DOI":"10.1038\/mt.2014.91","article-title":"Epigenetic manipulation restores functions of defective CD8(+) T cells from chronic viral infection","volume":"22","author":"Zhang","year":"2014","journal-title":"Mol Ther."},{"key":"B55","doi-asserted-by":"publisher","first-page":"3154","DOI":"10.1128\/JVI.02474-07","article-title":"High level of PD-1 expression on hepatitis C virus (HCV)-specific CD8+ and CD4+ T cells during acute HCV infection, irrespective of clinical outcome","volume":"82","author":"Kasprowicz","year":"2008","journal-title":"J Virol."},{"key":"B56","doi-asserted-by":"publisher","first-page":"334","DOI":"10.1159\/000456584","article-title":"Overcoming CD8+ T-cell exhaustion in viral hepatitis: lessons from the mouse model and clinical perspectives","volume":"35","author":"Wieland","year":"2017","journal-title":"Dig Dis."}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/article\/10.3389\/fimmu.2020.00372\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,3,10]],"date-time":"2020-03-10T06:02:42Z","timestamp":1583820162000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/article\/10.3389\/fimmu.2020.00372\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,3,10]]},"references-count":56,"alternative-id":["10.3389\/fimmu.2020.00372"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2020.00372","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,3,10]]},"article-number":"372"}}