{"id":"https://openalex.org/W2946876802","doi":"https://doi.org/10.1200/jco.2019.37.15_suppl.e20075","title":"Identifying small cell lung cancer resistance mechanisms to cytotoxic T cells in vitro using whole genome CRISPR screening.","display_name":"Identifying small cell lung cancer resistance mechanisms to cytotoxic T cells in vitro using whole genome CRISPR screening.","publication_year":2019,"publication_date":"2019-05-20","ids":{"openalex":"https://openalex.org/W2946876802","doi":"https://doi.org/10.1200/jco.2019.37.15_suppl.e20075","mag":"2946876802"},"language":"en","primary_location":{"id":"doi:10.1200/jco.2019.37.15_suppl.e20075","doi":"https://doi.org/10.1200/jco.2019.37.15_suppl.e20075","is_oa":false,"landing_page_url":"https://doi.org/10.1200/jco.2019.37.15_suppl.e20075","pdf_url":null,"source":{"id":"https://openalex.org/S15137598","display_name":"Journal of Clinical Oncology","issn_l":"0732-183X","issn":["0732-183X","1527-7755"],"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/P4310315671","host_organization_name":"Lippincott Williams & Wilkins","host_organization_lineage":["https://openalex.org/P4310315671","https://openalex.org/P4310318547"],"host_organization_lineage_names":["Lippincott Williams & Wilkins","Wolters Kluwer"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Journal of Clinical Oncology","raw_type":"journal-article"},"volume":null,"type":"conference-abstract","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/A5040242740","display_name":"Joseph B. Hiatt","orcid":"https://orcid.org/0000-0002-8050-5310","observed_orcids":["https://orcid.org/0000-0002-8050-5310"]},"institutions":[{"id":"https://openalex.org/I4210089486","display_name":"Fred Hutch Cancer Center","ror":"https://ror.org/007ps6h72","country_code":"US","type":"nonprofit","lineage":["https://openalex.org/I4210089486"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Joseph Hiatt","raw_affiliation_strings":["Fred Hutchinson Cancer Research Center, Seattle, WA;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Fred Hutchinson Cancer Research Center, Seattle, WA;","institution_ids":["https://openalex.org/I4210089486"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5090196149","display_name":"David P MacPherson","orcid":"https://orcid.org/0000-0003-3729-907X","observed_orcids":["https://orcid.org/0000-0003-3729-907X"]},"institutions":[{"id":"https://openalex.org/I4210089486","display_name":"Fred Hutch Cancer Center","ror":"https://ror.org/007ps6h72","country_code":"US","type":"nonprofit","lineage":["https://openalex.org/I4210089486"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"David MacPherson","raw_affiliation_strings":["Fred Hutchinson Cancer Research Center, Seattle, WA;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Fred Hutchinson Cancer Research Center, Seattle, WA;","institution_ids":["https://openalex.org/I4210089486"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"corresponding_author_ids":[],"corresponding_institution_ids":["https://openalex.org/I4210089486"],"apc_list":null,"apc_paid":null,"fwci":null,"has_fulltext":false,"cited_by_count":0,"citation_normalized_percentile":null,"cited_by_percentile_year":null,"biblio":{"volume":"37","issue":"15_suppl","first_page":"e20075","last_page":"e20075"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10158","display_name":"Cancer Immunotherapy and Biomarkers","score":0.6470000147819519,"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":0.6470000147819519,"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/T12334","display_name":"Lung Cancer Research Studies","score":0.3244999945163727,"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/T10580","display_name":"Immunotherapy and Immune Responses","score":0.0031999999191612005,"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"}}],"keywords":[{"id":"https://openalex.org/keywords/small-cell-lung-cancer","display_name":"small cell lung cancer","score":1.0},{"id":"https://openalex.org/keywords/immunotherapy-resistance","display_name":"immunotherapy resistance","score":0.6980000138282776},{"id":"https://openalex.org/keywords/crispr-screening","display_name":"CRISPR screen","score":0.7390000224113464},{"id":"https://openalex.org/keywords/tumor-mutational-burden","display_name":"tumor mutational burden","score":0.6629999876022339},{"id":"https://openalex.org/keywords/immune-checkpoint-blockade","display_name":"immune checkpoint blockade","score":0.7099999785423279},{"id":"https://openalex.org/keywords/antigen-presentation","display_name":"antigen presentation","score":0.5630000233650208},{"id":"https://openalex.org/keywords/nf-kb","display_name":"NF-kB","score":0.7490000128746033},{"id":"https://openalex.org/keywords/tumor-immunosuppression","display_name":"tumor immunosuppression","score":0.6330000162124634},{"id":"https://openalex.org/keywords/ot-i-t-cells","display_name":"OT-I T cells","score":0.5440000295639038},{"id":"https://openalex.org/keywords/ovalbumin-peptide","display_name":"ovalbumin peptide","score":0.6330000162124634}],"concepts":[{"id":"https://openalex.org/C154317977","wikidata":"https://www.wikidata.org/wiki/Q376266","display_name":"Cytotoxic T cell","level":3,"score":0.7241147756576538},{"id":"https://openalex.org/C502942594","wikidata":"https://www.wikidata.org/wiki/Q3421914","display_name":"Cancer research","level":1,"score":0.6316508650779724},{"id":"https://openalex.org/C167672396","wikidata":"https://www.wikidata.org/wiki/Q417800","display_name":"CD8","level":3,"score":0.5487663149833679},{"id":"https://openalex.org/C98108389","wikidata":"https://www.wikidata.org/wiki/Q412563","display_name":"CRISPR","level":3,"score":0.46395984292030334},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.46103739738464355},{"id":"https://openalex.org/C121608353","wikidata":"https://www.wikidata.org/wiki/Q12078","display_name":"Cancer","level":2,"score":0.44450709223747253},{"id":"https://openalex.org/C2780851360","wikidata":"https://www.wikidata.org/wiki/Q21686041","display_name":"Immune checkpoint","level":4,"score":0.42179906368255615},{"id":"https://openalex.org/C96232424","wikidata":"https://www.wikidata.org/wiki/Q4118072","display_name":"Cancer cell","level":3,"score":0.41960710287094116},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.3624223470687866},{"id":"https://openalex.org/C2777701055","wikidata":"https://www.wikidata.org/wiki/Q1427096","display_name":"Immunotherapy","level":3,"score":0.31108278036117554},{"id":"https://openalex.org/C8891405","wikidata":"https://www.wikidata.org/wiki/Q1059","display_name":"Immune system","level":2,"score":0.30924999713897705},{"id":"https://openalex.org/C203014093","wikidata":"https://www.wikidata.org/wiki/Q101929","display_name":"Immunology","level":1,"score":0.2894766628742218},{"id":"https://openalex.org/C104317684","wikidata":"https://www.wikidata.org/wiki/Q7187","display_name":"Gene","level":2,"score":0.24679476022720337},{"id":"https://openalex.org/C202751555","wikidata":"https://www.wikidata.org/wiki/Q221681","display_name":"In vitro","level":2,"score":0.22522735595703125},{"id":"https://openalex.org/C54355233","wikidata":"https://www.wikidata.org/wiki/Q7162","display_name":"Genetics","level":1,"score":0.14163604378700256}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.1200/jco.2019.37.15_suppl.e20075","doi":"https://doi.org/10.1200/jco.2019.37.15_suppl.e20075","is_oa":false,"landing_page_url":"https://doi.org/10.1200/jco.2019.37.15_suppl.e20075","pdf_url":null,"source":{"id":"https://openalex.org/S15137598","display_name":"Journal of Clinical Oncology","issn_l":"0732-183X","issn":["0732-183X","1527-7755"],"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/P4310315671","host_organization_name":"Lippincott Williams & Wilkins","host_organization_lineage":["https://openalex.org/P4310315671","https://openalex.org/P4310318547"],"host_organization_lineage_names":["Lippincott Williams & Wilkins","Wolters Kluwer"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Journal of Clinical Oncology","raw_type":"journal-article"}],"best_oa_location":null,"sustainable_development_goals":[{"display_name":"Good health and well-being","id":"https://metadata.un.org/sdg/3","score":1.0}],"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/W2891267334","https://openalex.org/W4323569975","https://openalex.org/W6965036359","https://openalex.org/W7130340787","https://openalex.org/W2942648292","https://openalex.org/W4214878846","https://openalex.org/W2324217946","https://openalex.org/W4409629222","https://openalex.org/W7065940677","https://openalex.org/W4313406885"],"abstract_inverted_index":{"e20075":[0],"Background:":[1],"Small":[2],"cell":[3,77,140,171,337],"lung":[4,78],"cancer":[5,111],"(SCLC)":[6],"is":[7,296],"a":[8,20,98,126,139,144,168,291],"highly":[9],"aggressive":[10],"neuroendocrine":[11],"neoplasm":[12],"associated":[13],"with":[14,35,50,63,173,193,200],"high":[15,36,175],"tumor":[16],"mutation":[17],"burden":[18],"(TMB),":[19],"paucity":[21],"of":[22,110,131,149,222,256,264,282,294],"compelling":[23],"therapeutic":[24,92],"options,":[25],"and":[26,46,61,91,125,156,198,212,260,270,298,303,324,333],"very":[27,174],"poor":[28],"survival.":[29],"In":[30,152],"comparison":[31],"to":[32,41,102,113,217,308,310,335],"other":[33],"malignancies":[34],"TMB,":[37],"SCLC":[38,150,295],"patients":[39],"tend":[40],"experience":[42],"lower":[43],"response":[44,48],"rates":[45],"shorter":[47],"durations":[49],"immune":[51],"checkpoint":[52],"blockade":[53],"(ICB)":[54],"targeting":[55],"the":[56,71,108,162,178,219],"PD-1":[57],"and/or":[58],"CTLA-4":[59],"axes,":[60],"chemotherapy":[62],"ICB":[64],"in":[65,75,94,224,283,290,312,322,325],"first":[66],"line":[67,141],"does":[68],"not":[69],"exhibit":[70],"dramatic":[72],"synergy":[73],"seen":[74],"non-small":[76],"cancer.":[79],"To":[80],"identify":[81],"additional":[82,336],"immunosuppressive":[83],"mechanisms":[84],"that":[85,106,300],"could":[86],"serve":[87],"as":[88],"novel":[89,304],"biomarkers":[90],"targets":[93],"SCLC,":[95],"we":[96,154,231],"adapted":[97],"recently":[99],"described":[100],"method":[101],"screen":[103],"for":[104,177,203,280],"genes":[105],"alter":[107],"sensitivity":[109],"cells":[112,160,190,202,289],"killing":[114,242,285],"by":[115,243,286],"cytotoxic":[116],"CD8+":[117,158,244,287],"T":[118,159,170,201,245,288],"cells.":[119,246],"Methods:":[120],"We":[121,206,248],"introduced":[122],"Cas9":[123],"nuclease":[124],"genome-wide":[127],"gene":[128,234,330],"inactivation":[129],"library":[130],"~80,000":[132],"single":[133],"guide":[134],"RNA":[135],"(sgRNA)":[136],"templates":[137],"into":[138],"derived":[142],"from":[143,161],"genetically":[145],"engineered":[146],"murine":[147,292],"model":[148,293],"(mSCLC).":[151],"parallel,":[153],"isolated":[155,210],"stimulated":[157],"OT-I":[163],"transgenic":[164],"mouse,":[165],"which":[166,233],"express":[167],"rearranged":[169],"receptor":[172],"avidity":[176],"ovalbumin":[179],"(OVA)":[180],"SIINFEKL":[181],"peptide":[182,195],"presented":[183],"on":[184],"H2-K(b)":[185],"class":[186],"I":[187],"MHC.":[188],"mSCLC":[189],"were":[191,236],"loaded":[192],"OVA":[194],"or":[196,239],"vehicle":[197],"co-cultured":[199],"24":[204],"hours.":[205],"collected":[207],"surviving":[208],"cells,":[209],"DNA,":[211],"used":[213],"next-generation":[214],"DNA":[215],"sequencing":[216],"tabulate":[218],"relative":[220],"representation":[221],"sgRNAs":[223],"each":[225],"experimental":[226],"condition.":[227],"From":[228],"these":[229,320],"data,":[230],"inferred":[232],"knockouts":[235],"protective":[237],"from,":[238],"sensitizing":[240],"to,":[241],"Results:":[247],"observed":[249],"expected":[250,302],"mediators,":[251],"including":[252],"resistance":[253,309],"via":[254,262],"knockout":[255,263],"antigen":[257],"presentation":[258],"machinery":[259],"sensitization":[261],"pro-survival":[265],"pathways":[266,305],"(":[267],"e.g.":[268],"NF-kB),":[269],"unexpected":[271],"hits":[272,321],"spanning":[273],"diverse":[274],"cellular":[275],"functions.":[276],"Conclusions:":[277],"Genome-wide":[278],"screening":[279],"mediators":[281],"vitro":[284,323],"feasible":[297],"reveals":[299],"both":[301],"may":[306],"contribute":[307],"immunotherapy":[311],"SCLC.":[313],"Future":[314],"studies":[315],"are":[316],"directed":[317],"at":[318],"validating":[319],"vivo,":[326],"incorporating":[327],"new":[328],"complex":[329],"perturbation":[331],"libraries,":[332],"scaling":[334],"lines.":[338]},"counts_by_year":[],"updated_date":"2026-09-22T06:50:58.402377","created_date":"2019-06-07T00:00:00"}
