{"id":"https://openalex.org/W2986516670","doi":"https://doi.org/10.1182/blood-2019-130647","title":"Evaluation of T-Cell Compartment By Complex Multiparameter Flow Cytometry Reveals Distinct Patterns of T-Cell Exhaustion in DLBCL, FL and HL Patients","display_name":"Evaluation of T-Cell Compartment By Complex Multiparameter Flow Cytometry Reveals Distinct Patterns of T-Cell Exhaustion in DLBCL, FL and HL Patients","publication_year":2019,"publication_date":"2019-11-13","ids":{"openalex":"https://openalex.org/W2986516670","doi":"https://doi.org/10.1182/blood-2019-130647","mag":"2986516670"},"language":"en","primary_location":{"id":"doi:10.1182/blood-2019-130647","doi":"https://doi.org/10.1182/blood-2019-130647","is_oa":false,"landing_page_url":"https://doi.org/10.1182/blood-2019-130647","pdf_url":null,"source":{"id":"https://openalex.org/S200071133","display_name":"Blood","issn_l":"0006-4971","issn":["0006-4971","1528-0020"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","dongbi-a","doyens","jufo-3","ki-jl-3","medline","norway-2","poland-200","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320990","host_organization_name":"Elsevier BV","host_organization_lineage":["https://openalex.org/P4310320990"],"host_organization_lineage_names":["Elsevier BV"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Blood","raw_type":"journal-article"},"volume":null,"type":"conference-abstract","is_traditional":false,"indexed_in":["crossref"],"open_access":{"is_oa":false,"oa_status":"closed","oa_url":null,"any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5011957269","display_name":"Alexis Vall\u00e9e","orcid":"https://orcid.org/0009-0008-7761-5368","observed_orcids":["https://orcid.org/0009-0008-7761-5368"]},"institutions":[{"id":"https://openalex.org/I4405268511","display_name":"CHU Sainte-Justine Research Center","ror":"https://ror.org/016e4fa89","country_code":"CA","type":"facility","lineage":["https://openalex.org/I4405268511"]},{"id":"https://openalex.org/I70931966","display_name":"Universit\u00e9 de Montr\u00e9al","ror":"https://ror.org/0161xgx34","country_code":"CA","type":"education","lineage":["https://openalex.org/I70931966"]}],"countries":["CA"],"is_corresponding":false,"raw_author_name":"Alexis Vall\u00e9e","raw_affiliation_strings":["CHU Sainte-Justine Research Center, University of Montreal, Montreal, Canada"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"CHU Sainte-Justine Research Center, University of Montreal, Montreal, Canada","institution_ids":["https://openalex.org/I4405268511","https://openalex.org/I70931966"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5003417366","display_name":"Mitra Shourian","orcid":"https://orcid.org/0009-0001-6803-6291","observed_orcids":["https://orcid.org/0009-0001-6803-6291"]},"institutions":[{"id":"https://openalex.org/I4405268511","display_name":"CHU Sainte-Justine Research Center","ror":"https://ror.org/016e4fa89","country_code":"CA","type":"facility","lineage":["https://openalex.org/I4405268511"]},{"id":"https://openalex.org/I70931966","display_name":"Universit\u00e9 de Montr\u00e9al","ror":"https://ror.org/0161xgx34","country_code":"CA","type":"education","lineage":["https://openalex.org/I70931966"]}],"countries":["CA"],"is_corresponding":false,"raw_author_name":"Mitra Shourian","raw_affiliation_strings":["CHU Sainte-Justine Research Center, University of Montreal, Montreal, Canada"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"CHU Sainte-Justine Research Center, University of Montreal, Montreal, Canada","institution_ids":["https://openalex.org/I4405268511","https://openalex.org/I70931966"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5039588431","display_name":"Nathalie A. Johnson","orcid":"https://orcid.org/0000-0002-3211-9722","observed_orcids":["https://orcid.org/0000-0002-3211-9722"]},"institutions":[{"id":"https://openalex.org/I5023651","display_name":"McGill University","ror":"https://ror.org/01pxwe438","country_code":"CA","type":"education","lineage":["https://openalex.org/I5023651"]}],"countries":["CA"],"is_corresponding":false,"raw_author_name":"Nathalie Johnson","raw_affiliation_strings":["McGill University, Montreal, Canada"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"McGill University, Montreal, Canada","institution_ids":["https://openalex.org/I5023651"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5000732151","display_name":"H\u00e9l\u00e8ne Decaluwe","orcid":"https://orcid.org/0000-0001-6617-0633","observed_orcids":["https://orcid.org/0000-0001-6617-0633"]},"institutions":[{"id":"https://openalex.org/I4405268511","display_name":"CHU Sainte-Justine Research Center","ror":"https://ror.org/016e4fa89","country_code":"CA","type":"facility","lineage":["https://openalex.org/I4405268511"]},{"id":"https://openalex.org/I70931966","display_name":"Universit\u00e9 de Montr\u00e9al","ror":"https://ror.org/0161xgx34","country_code":"CA","type":"education","lineage":["https://openalex.org/I70931966"]}],"countries":["CA"],"is_corresponding":false,"raw_author_name":"H\u00e9l\u00e8ne Decaluwe","raw_affiliation_strings":["CHU Sainte-Justine Research Center, Universit\u00e9 De Montr\u00e9al, Montreal, Canada"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"CHU Sainte-Justine Research Center, Universit\u00e9 De Montr\u00e9al, Montreal, Canada","institution_ids":["https://openalex.org/I4405268511","https://openalex.org/I70931966"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":3,"corresponding_author_ids":[],"corresponding_institution_ids":[],"apc_list":{"value":5500,"currency":"USD","value_usd":5500},"apc_paid":null,"fwci":null,"has_fulltext":false,"cited_by_count":1,"citation_normalized_percentile":null,"cited_by_percentile_year":null,"biblio":{"volume":"134","issue":"Supplement_1","first_page":"2806","last_page":"2806"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10158","display_name":"Cancer Immunotherapy and Biomarkers","score":0.7803000211715698,"subfield":{"id":"https://openalex.org/subfields/2730","display_name":"Oncology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},"topics":[{"id":"https://openalex.org/T10158","display_name":"Cancer Immunotherapy and Biomarkers","score":0.7803000211715698,"subfield":{"id":"https://openalex.org/subfields/2730","display_name":"Oncology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T10031","display_name":"T-cell and B-cell Immunology","score":0.12780000269412994,"subfield":{"id":"https://openalex.org/subfields/2403","display_name":"Immunology"},"field":{"id":"https://openalex.org/fields/24","display_name":"Immunology and Microbiology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T10185","display_name":"Lymphoma Diagnosis and Treatment","score":0.06279999762773514,"subfield":{"id":"https://openalex.org/subfields/2734","display_name":"Pathology and Forensic Medicine"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/t-cell-exhaustion","display_name":"T cell exhaustion","score":0.9350000023841858},{"id":"https://openalex.org/keywords/immune-checkpoint-blockade","display_name":"immune checkpoint blockade","score":0.7409999966621399},{"id":"https://openalex.org/keywords/pd-1","display_name":"PD-1","score":0.7839999794960022},{"id":"https://openalex.org/keywords/tim-3","display_name":"TIM-3","score":0.6779999732971191},{"id":"https://openalex.org/keywords/lag-3","display_name":"LAG-3","score":0.8479999899864197},{"id":"https://openalex.org/keywords/diffuse-large-b-cell-lymphoma","display_name":"diffuse large B-cell lymphoma","score":0.8379999995231628},{"id":"https://openalex.org/keywords/follicular-lymphoma","display_name":"follicular lymphoma","score":1.0},{"id":"https://openalex.org/keywords/hodgkin-lymphoma","display_name":"Hodgkin's disease","score":0.9919999837875366},{"id":"https://openalex.org/keywords/tumor-infiltrating-lymphocytes","display_name":"tumor-infiltrating lymphocytes","score":0.9399999976158142},{"id":"https://openalex.org/keywords/cd8-t-cells","display_name":"CD8+ T cells","score":0.8970000147819519},{"id":"https://openalex.org/keywords/anti-pd-1-resistance","display_name":"anti-PD-1 resistance","score":0.5929999947547913}],"concepts":[{"id":"https://openalex.org/C2779338263","wikidata":"https://www.wikidata.org/wiki/Q208414","display_name":"Lymphoma","level":2,"score":0.5997087955474854},{"id":"https://openalex.org/C196166836","wikidata":"https://www.wikidata.org/wiki/Q902926","display_name":"Immunophenotyping","level":3,"score":0.5797273516654968},{"id":"https://openalex.org/C167672396","wikidata":"https://www.wikidata.org/wiki/Q417800","display_name":"CD8","level":3,"score":0.5401548147201538},{"id":"https://openalex.org/C502942594","wikidata":"https://www.wikidata.org/wiki/Q3421914","display_name":"Cancer research","level":1,"score":0.5207974314689636},{"id":"https://openalex.org/C2776090121","wikidata":"https://www.wikidata.org/wiki/Q193529","display_name":"T cell","level":3,"score":0.5112066268920898},{"id":"https://openalex.org/C2777058707","wikidata":"https://www.wikidata.org/wiki/Q123251","display_name":"Follicular lymphoma","level":3,"score":0.5048967003822327},{"id":"https://openalex.org/C2778559949","wikidata":"https://www.wikidata.org/wiki/Q2626074","display_name":"Diffuse large B-cell lymphoma","level":3,"score":0.4848998188972473},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.48327523469924927},{"id":"https://openalex.org/C553184892","wikidata":"https://www.wikidata.org/wiki/Q1141429","display_name":"Flow cytometry","level":2,"score":0.4416426718235016},{"id":"https://openalex.org/C2777701055","wikidata":"https://www.wikidata.org/wiki/Q1427096","display_name":"Immunotherapy","level":3,"score":0.4186880886554718},{"id":"https://openalex.org/C203014093","wikidata":"https://www.wikidata.org/wiki/Q101929","display_name":"Immunology","level":1,"score":0.3924627900123596},{"id":"https://openalex.org/C143998085","wikidata":"https://www.wikidata.org/wiki/Q162555","display_name":"Oncology","level":1,"score":0.35644012689590454},{"id":"https://openalex.org/C126322002","wikidata":"https://www.wikidata.org/wiki/Q11180","display_name":"Internal medicine","level":1,"score":0.3258242607116699},{"id":"https://openalex.org/C8891405","wikidata":"https://www.wikidata.org/wiki/Q1059","display_name":"Immune system","level":2,"score":0.31008180975914}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.1182/blood-2019-130647","doi":"https://doi.org/10.1182/blood-2019-130647","is_oa":false,"landing_page_url":"https://doi.org/10.1182/blood-2019-130647","pdf_url":null,"source":{"id":"https://openalex.org/S200071133","display_name":"Blood","issn_l":"0006-4971","issn":["0006-4971","1528-0020"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","dongbi-a","doyens","jufo-3","ki-jl-3","medline","norway-2","poland-200","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320990","host_organization_name":"Elsevier BV","host_organization_lineage":["https://openalex.org/P4310320990"],"host_organization_lineage_names":["Elsevier BV"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Blood","raw_type":"journal-article"}],"best_oa_location":null,"sustainable_development_goals":[{"score":0.9763000011444092,"display_name":"Good health and well-being","id":"https://metadata.un.org/sdg/3"}],"study_designs":[],"awards":[],"funders":[],"has_content":{"grobid_xml":false,"pdf":false},"content_urls":null,"referenced_works_count":0,"referenced_works":[],"related_works":["https://openalex.org/W4319432270","https://openalex.org/W4280590126","https://openalex.org/W2984622414","https://openalex.org/W2954714704","https://openalex.org/W2972766433","https://openalex.org/W3146399486","https://openalex.org/W2949335654","https://openalex.org/W2911487711","https://openalex.org/W4281718779","https://openalex.org/W3202615802"],"abstract_inverted_index":{"Background:":[0],"Immune":[1],"checkpoint":[2],"(IC)":[3],"blockade":[4,32,89],"has":[5,14],"revolutionized":[6],"the":[7,19,35,72,107,282,415,423,452,580,609,767],"treatment":[8,20],"of":[9,21,37,46,56,74,109,123,128,136,158,201,248,284,302,317,333,358,378,385,410,414,458,496,531,543,579,612,724,746,766,774,787],"chemo-refractory":[10],"solid":[11],"tumors":[12],"and":[13,62,78,152,160,181,212,257,263,265,270,275,287,296,320,339,346,364,367,382,394,412,419,441,446,454,468,481,505,510,524,591,593,619,733,796],"demonstrated":[15,550,568],"promising":[16],"results":[17,216,575],"for":[18,597],"resistant":[22],"blood":[23],"cancers,":[24],"including":[25],"lymphoma.":[26],"However,":[27],"clinical":[28,572],"response":[29],"to":[30,54,87,116,140,168,225,273,310,343,439,466,551,554,569],"PD1":[31,88,253],"depends":[33],"on":[34,720,742,783],"subtype":[36],"lymphoma,":[38],"with":[39,191,219,329,355,380,388,493,545,571],"durable":[40],"responses":[41],"observed":[42,429],"in":[43,76,337,361,463,501,589,599,631,770],"70":[44],"%":[45],"Hodgkin":[47],"lymphoma":[48,176],"(HL)":[49],"patients":[50,154,190,244,277,341,526,540,559],"versus":[51],"only":[52],"36":[53],"40%":[55],"Diffuse":[57],"Large":[58],"B-Cell":[59],"Lymphoma":[60,64],"(DLBCL)":[61],"Follicular":[63],"(FL)":[65],"patients(1-3).":[66],"The":[67,120,215],"biological":[68],"aspects":[69],"that":[70,148,239,294,305,430,520,533],"hinder":[71],"efficacy":[73],"immunotherapy":[75],"DLBCL":[77,151,243,295,338,363,431,464,502,523,558,590],"FL":[79,153,193,274,297,340,365,440,467,504,525,592],"patient":[80],"are":[81,405,420],"not":[82],"well-known.":[83],"Primary":[84],"tumor":[85],"resistance":[86],"could":[90],"be":[91,552],"driven":[92,421],"by":[93,98,407,422,608],"inherent":[94],"genomic":[95],"alterations":[96],"or":[97,194,726,748,789],"ineffective":[99],"anti-tumor":[100,142,585],"T":[101,130,143,335,403,499,586],"cell":[102,144,186,587],"responses.":[103],"ICs":[104,124,138,159,250,532],"expressed":[105],"at":[106,179],"surface":[108],"tumor-infiltrating-lymphocytes":[110],"(TILs)":[111],"use":[112],"distinct":[113],"suppressive":[114,536],"mechanisms":[115],"enforce":[117],"T-cell":[118,563],"dysfunction.":[119],"collective":[121],"expression":[122,283,409,413],"defines":[125],"multiple":[126,135],"subsets":[127,542,549,564],"exhausted":[129,165,401],"cells":[131,304,336,360,379,404,437,500,544],"during":[132],"cancer(4).":[133],"Since":[134],"these":[137,539],"collaborate":[139],"repress":[141],"functions,":[145],"we":[146],"hypothesized":[147],"TILs":[149,169,202,241,521],"from":[150,170,188,242,522],"express":[155,245,527],"high":[156],"levels":[157,247],"present":[161,541],"a":[162,184,299,313,528,763],"more":[163,314],"advanced":[164,315],"phenotype":[166],"compared":[167,272,309,342,438,465],"HL":[171,276,344,442,469,506],"patients.":[172],"Methods:":[173],"We":[174,196,428],"studied":[175],"samples":[177],"collected":[178],"diagnosis":[180],"frozen":[182],"as":[183,252],"viable":[185],"suspension":[187],"57":[189],"HL,":[192,311],"DLBCL.":[195],"performed":[197,232],"an":[198,330,721,743,784],"extended":[199],"immunophenotype":[200],"through":[203],"flow":[204],"cytometry":[205],"using":[206,233],"maturation":[207],"markers,":[208,210],"exhaustion":[209,318,387],"homing":[211],"chemokine":[213,416],"receptors.":[214],"were":[217,231,289,566],"analyzed":[218],"FlowJo.":[220],"Boolean":[221,291],"gating":[222],"was":[223,460],"used":[224,769],"assess":[226],"IC":[227],"co-expression.":[228],"Statistical":[229],"analyses":[230],"Prism.":[234],"Results:":[235],"Our":[236],"data":[237,491,518],"indicated":[238],"CD8":[240,402,498],"higher":[246,300],"classical":[249],"such":[251],"(1059":[254],"vs":[255,261,268,322,348,369,444,475,503,508],"1015":[256],"648),":[258],"Tim3":[259],"(1747":[260],"868":[262],"918,)":[264],"Lag3":[266],"(2603":[267],"1013":[269],"1031)":[271],"(p-value":[278],"<":[279,325,351,372,449,488,513],"0.01),":[280],"while":[281],"2B4,":[285],"BTLA":[286],"CD160":[288],"similar.":[290],"analysis":[292],"revealed":[293],"had":[298],"frequency":[301,332,357,453,495],"CD8T":[303],"co-expressed":[306],"6-7":[307],"ICs,":[308],"suggesting":[312],"state":[316],"(19%":[319],"26%":[321],"14%,":[323,349],"p-value":[324,350,371,448,487,512],"0.05).":[326],"This":[327,490,604],"correlated":[328,354,492],"increased":[331,356,546],"PD-1highCD39high":[334],"(32%":[345],"24%":[347],"0.005),":[352],"which":[353,565],"EOMEShigh":[359],"both":[362],"(84%":[366],"76%":[368],"55%,":[370],"0.005).":[373],"These":[374,574],"markers":[375],"identify":[376],"populations":[377],"phenotypic":[381],"transcriptomic":[383],"profiles":[384],"terminal":[386],"reduced":[389,462],"cytokine":[390],"production,":[391],"proliferative":[392],"capacity":[393],"persistence":[395],"(5,":[396],"6).":[397],"In":[398],"contrast,":[399],"stem-like":[400,562],"defined":[406],"intermediate":[408],"PD-1":[411,555],"receptor":[417],"CXCR5,":[418],"transcription":[424],"factor":[425],"TCF-1(7,":[426],"8).":[427],"exhibited":[432],"significantly":[433,461],"less":[434],"progenitor":[435],"Tim3-/CXCR5+":[436],"(27%":[443],"52%":[445],"40%,":[447],"0.01).":[450,489,514],"Further,":[451,538,557],"mean":[455],"fluorescent":[456],"intensity":[457],"TCF-1":[459],"(43%":[470],"/":[471,477,483],"495":[472],"\u00b1":[473,479,485],"64":[474],"70%":[476],"752":[478],"42":[480],"61%":[482],"670":[484],"74,":[486],"lower":[494],"CD27+":[497],"(82%":[507],"96%":[509],"96%,":[511],"Conclusion:":[515],"Collectively,":[516],"our":[517,577],"indicate":[519],"whole":[529],"array":[530],"have":[534],"non-redundant":[535],"functions.":[537],"functional":[547],"exhaustion,":[548],"unresponsive":[553],"blockade(7).":[556],"lack":[560],"protective":[561],"recently":[567],"correlate":[570],"outcome(9).":[573],"enlighten":[576],"knowledge":[578],"cellular":[581],"defects":[582],"precluding":[583],"potent":[584],"functions":[588],"propose":[594],"novel":[595],"targets":[596],"immunotherapies":[598],"PD-1-unresponsive":[600],"lymphomas.":[601],"Research":[602,614,735,751,798],"funding:":[603],"work":[605],"is":[606],"supported":[607],"Canadian":[610,616],"Institutes":[611],"Health":[613],"(PJT-155996),":[615],"Cancer":[617],"Society":[618],"Cole":[620],"Foundation":[621],"(grant":[622],"#705478).":[623],"References:":[624],"1.":[625],"S.":[626,688],"M.":[627,651,669,706],"Ansell":[628],"et":[629,642,653,663,672,681,691,700,708],"al.,":[630,643,654,664,673,682,692,701,709],"N":[632],"Engl":[633],"J":[634,644,655],"Med":[635],"372,":[636],"311":[637],"(2015).":[638,686],"2.":[639],"R.":[640],"Chen":[641],"Clin":[645,656],"Oncol35,":[646],"2125":[647],"(2017).":[648],"3.":[649],"A.":[650,670],"Lesokhin":[652],"Oncol34,":[657],"2698":[658],"(2016).":[659,695,704],"4.":[660],"B.":[661],"Bengsch":[662],"Immunity48,":[665],"1029":[666],"(2018).":[667],"5.":[668],"Paley":[671],"Science338,":[674],"1220":[675],"(2012).":[676],"6.":[677],"P.":[678],"K.":[679],"Gupta":[680],"PLoS":[683],"pathogens11,":[684],"e1005177":[685],"7.":[687],"J.":[689],"Im":[690],"Nature537,":[693],"417":[694],"8.":[696],"D.":[697],"T.":[698],"Utzschneider":[699],"Immunity45,":[702],"415":[703],"9.":[705],"Sade-Feldman":[707],"Cell176,":[710],"404":[711],"(2019).":[712],"Disclosures":[713],"Johnson:":[714],"Roche:":[715],"Consultancy,":[716,738,754,757],"Employment,":[717,739,780],"Honoraria,":[718,740,781],"Membership":[719,741,782],"entity's":[722,744,785],"Board":[723,745,786],"Directors":[725,747,788],"advisory":[727,749,790],"committees,":[728,750,791],"Other:":[729,761,792],"Travel":[730,793],"fees,":[731,794],"gifts,":[732,795],"others,":[734,797],"Funding;":[736,752],"Abbvie:":[737],"Merck:":[753],"Honoraria;":[755,758,778],"BMS:":[756],"BD":[759],"Biosciences:":[760],"Provided":[762],"significant":[764],"proportion":[765],"antibodies":[768],"this":[771],"project":[772],"free":[773],"cost.;":[775],"Seattle":[776],"Genetics:":[777],"Lundbeck:":[779],"Funding.":[799]},"counts_by_year":[{"year":2020,"cited_by_count":1}],"updated_date":"2026-09-25T08:18:29.962427","created_date":"2019-11-22T00:00:00"}
