{"id":"https://openalex.org/W4282960760","doi":"https://doi.org/10.1158/1538-7445.am2022-1386","title":"Abstract 1386: MAPK inhibition remodels antigen presentation in pancreatic ductal adenocarcinoma","display_name":"Abstract 1386: MAPK inhibition remodels antigen presentation in pancreatic ductal adenocarcinoma","publication_year":2022,"publication_date":"2022-06-15","ids":{"openalex":"https://openalex.org/W4282960760","doi":"https://doi.org/10.1158/1538-7445.am2022-1386"},"language":"en","primary_location":{"id":"doi:10.1158/1538-7445.am2022-1386","doi":"https://doi.org/10.1158/1538-7445.am2022-1386","is_oa":false,"landing_page_url":"https://doi.org/10.1158/1538-7445.am2022-1386","pdf_url":null,"source":{"id":"https://openalex.org/S168522863","display_name":"Cancer Research","issn_l":"0008-5472","issn":["0008-5472","1538-7445"],"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/P4310320273","host_organization_name":"American Association for Cancer Research","host_organization_lineage":["https://openalex.org/P4310320273"],"host_organization_lineage_names":["American Association for Cancer Research"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Cancer Research","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/A5000758436","display_name":"Amanda L. Creech","orcid":"https://orcid.org/0000-0002-8341-1213","observed_orcids":["https://orcid.org/0000-0002-8341-1213"]},"institutions":[{"id":"https://openalex.org/I161318765","display_name":"University of California, Los Angeles","ror":"https://ror.org/046rm7j60","country_code":"US","type":"education","lineage":["https://openalex.org/I161318765"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Amanda L. Creech","raw_affiliation_strings":["1UCLA David Geffen School of Medicine, Los Angeles, CA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1UCLA David Geffen School of Medicine, Los Angeles, CA","institution_ids":["https://openalex.org/I161318765"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5001373227","display_name":"Thuc M. Le","orcid":"https://orcid.org/0000-0003-2364-9374","observed_orcids":["https://orcid.org/0000-0003-2364-9374"]},"institutions":[{"id":"https://openalex.org/I161318765","display_name":"University of California, Los Angeles","ror":"https://ror.org/046rm7j60","country_code":"US","type":"education","lineage":["https://openalex.org/I161318765"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Thuc M. Le","raw_affiliation_strings":["1UCLA David Geffen School of Medicine, Los Angeles, CA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1UCLA David Geffen School of Medicine, Los Angeles, CA","institution_ids":["https://openalex.org/I161318765"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5066633792","display_name":"Evan R. Abt","orcid":"https://orcid.org/0000-0002-3160-7134","observed_orcids":["https://orcid.org/0000-0002-3160-7134"]},"institutions":[{"id":"https://openalex.org/I161318765","display_name":"University of California, Los Angeles","ror":"https://ror.org/046rm7j60","country_code":"US","type":"education","lineage":["https://openalex.org/I161318765"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Evan R. Abt","raw_affiliation_strings":["1UCLA David Geffen School of Medicine, Los Angeles, CA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1UCLA David Geffen School of Medicine, Los Angeles, CA","institution_ids":["https://openalex.org/I161318765"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5112554258","display_name":"Joseph R. Capri","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I161318765","display_name":"University of California, Los Angeles","ror":"https://ror.org/046rm7j60","country_code":"US","type":"education","lineage":["https://openalex.org/I161318765"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Joseph R. Capri","raw_affiliation_strings":["1UCLA David Geffen School of Medicine, Los Angeles, CA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1UCLA David Geffen School of Medicine, Los Angeles, CA","institution_ids":["https://openalex.org/I161318765"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5058851560","display_name":"Timothy R. Donahue","orcid":"https://orcid.org/0000-0002-1175-2545","observed_orcids":["https://orcid.org/0000-0002-1175-2545"]},"institutions":[{"id":"https://openalex.org/I161318765","display_name":"University of California, Los Angeles","ror":"https://ror.org/046rm7j60","country_code":"US","type":"education","lineage":["https://openalex.org/I161318765"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Timothy R. Donahue","raw_affiliation_strings":["1UCLA David Geffen School of Medicine, Los Angeles, CA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1UCLA David Geffen School of Medicine, Los Angeles, CA","institution_ids":["https://openalex.org/I161318765"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5018755772","display_name":"Caius G. Radu","orcid":"https://orcid.org/0000-0002-9338-5397","observed_orcids":["https://orcid.org/0000-0002-9338-5397"]},"institutions":[{"id":"https://openalex.org/I161318765","display_name":"University of California, Los Angeles","ror":"https://ror.org/046rm7j60","country_code":"US","type":"education","lineage":["https://openalex.org/I161318765"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Caius G. Radu","raw_affiliation_strings":["1UCLA David Geffen School of Medicine, Los Angeles, CA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1UCLA David Geffen School of Medicine, Los Angeles, CA","institution_ids":["https://openalex.org/I161318765"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"corresponding_author_ids":[],"corresponding_institution_ids":["https://openalex.org/I161318765"],"apc_list":null,"apc_paid":null,"fwci":null,"has_fulltext":false,"cited_by_count":1,"citation_normalized_percentile":null,"cited_by_percentile_year":null,"biblio":{"volume":"82","issue":"12_Supplement","first_page":"1386","last_page":"1386"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10231","display_name":"Pancreatic and Hepatic Oncology Research","score":0.7699999809265137,"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/T10231","display_name":"Pancreatic and Hepatic Oncology Research","score":0.7699999809265137,"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/T10158","display_name":"Cancer Immunotherapy and Biomarkers","score":0.14229999482631683,"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":0.05380000174045563,"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/pancreatic-ductal-adenocarcinoma","display_name":"pancreatic ductal adenocarcinoma","score":1.0},{"id":"https://openalex.org/keywords/mapk-signaling","display_name":"MAPK signaling","score":0.7649999856948853},{"id":"https://openalex.org/keywords/kras-inhibition","display_name":"KRAS inhibition","score":0.7419999837875366},{"id":"https://openalex.org/keywords/shp2-inhibition","display_name":"SHP2 inhibition","score":0.9570000171661377},{"id":"https://openalex.org/keywords/mek-inhibition","display_name":"MEK inhibition","score":0.902999997138977},{"id":"https://openalex.org/keywords/antigen-presentation","display_name":"antigen presentation","score":0.902999997138977},{"id":"https://openalex.org/keywords/mhc-class-i","display_name":"MHC class I","score":0.8029999732971191},{"id":"https://openalex.org/keywords/pd-l1","display_name":"PD-L1","score":0.9610000252723694},{"id":"https://openalex.org/keywords/tumor-associated-antigens","display_name":"tumor-associated antigens","score":0.8389999866485596},{"id":"https://openalex.org/keywords/mesothelin","display_name":"mesothelin","score":0.9850000143051147},{"id":"https://openalex.org/keywords/prostate-stem-cell-antigen","display_name":"prostate stem cell antigen","score":1.0},{"id":"https://openalex.org/keywords/immunopeptidomics","display_name":"immunopeptidomics","score":0.9200000166893005},{"id":"https://openalex.org/keywords/type-i-interferon","display_name":"type I interferon","score":0.8949999809265137},{"id":"https://openalex.org/keywords/immunosuppressive-tumor-microenvironment","display_name":"immunosuppressive tumor microenvironment","score":0.7590000033378601},{"id":"https://openalex.org/keywords/cancer-immunotherapy","display_name":"cancer immunotherapy","score":0.6190000176429749},{"id":"https://openalex.org/keywords/kras-g12c","display_name":"KRAS G12C","score":0.8029999732971191}],"concepts":[{"id":"https://openalex.org/C2781187634","wikidata":"https://www.wikidata.org/wiki/Q20969980","display_name":"KRAS","level":4,"score":0.8258287906646729},{"id":"https://openalex.org/C502942594","wikidata":"https://www.wikidata.org/wiki/Q3421914","display_name":"Cancer research","level":1,"score":0.6849571466445923},{"id":"https://openalex.org/C57074206","wikidata":"https://www.wikidata.org/wiki/Q14197552","display_name":"MAPK/ERK pathway","level":3,"score":0.5827224850654602},{"id":"https://openalex.org/C83464605","wikidata":"https://www.wikidata.org/wiki/Q575296","display_name":"Antigen presentation","level":4,"score":0.537857174873352},{"id":"https://openalex.org/C2776107976","wikidata":"https://www.wikidata.org/wiki/Q1786433","display_name":"Tumor microenvironment","level":3,"score":0.5332369804382324},{"id":"https://openalex.org/C2781249067","wikidata":"https://www.wikidata.org/wiki/Q17142288","display_name":"MEK inhibitor","level":4,"score":0.4567888379096985},{"id":"https://openalex.org/C147483822","wikidata":"https://www.wikidata.org/wiki/Q103537","display_name":"Antigen","level":2,"score":0.4413529634475708},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.4161161780357361},{"id":"https://openalex.org/C8891405","wikidata":"https://www.wikidata.org/wiki/Q1059","display_name":"Immune system","level":2,"score":0.36365485191345215},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.3628137707710266},{"id":"https://openalex.org/C62478195","wikidata":"https://www.wikidata.org/wiki/Q828130","display_name":"Signal transduction","level":2,"score":0.301879346370697},{"id":"https://openalex.org/C203014093","wikidata":"https://www.wikidata.org/wiki/Q101929","display_name":"Immunology","level":1,"score":0.29698824882507324},{"id":"https://openalex.org/C2776090121","wikidata":"https://www.wikidata.org/wiki/Q193529","display_name":"T cell","level":3,"score":0.22417721152305603},{"id":"https://openalex.org/C121608353","wikidata":"https://www.wikidata.org/wiki/Q12078","display_name":"Cancer","level":2,"score":0.2208719551563263},{"id":"https://openalex.org/C95444343","wikidata":"https://www.wikidata.org/wiki/Q7141","display_name":"Cell biology","level":1,"score":0.16294249892234802},{"id":"https://openalex.org/C126322002","wikidata":"https://www.wikidata.org/wiki/Q11180","display_name":"Internal medicine","level":1,"score":0.1420038342475891},{"id":"https://openalex.org/C526805850","wikidata":"https://www.wikidata.org/wiki/Q188874","display_name":"Colorectal cancer","level":3,"score":0.07689085602760315},{"id":"https://openalex.org/C3020616263","wikidata":"https://www.wikidata.org/wiki/Q1216998","display_name":"Tumor cells","level":2,"score":0.0}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.1158/1538-7445.am2022-1386","doi":"https://doi.org/10.1158/1538-7445.am2022-1386","is_oa":false,"landing_page_url":"https://doi.org/10.1158/1538-7445.am2022-1386","pdf_url":null,"source":{"id":"https://openalex.org/S168522863","display_name":"Cancer Research","issn_l":"0008-5472","issn":["0008-5472","1538-7445"],"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/P4310320273","host_organization_name":"American Association for Cancer Research","host_organization_lineage":["https://openalex.org/P4310320273"],"host_organization_lineage_names":["American Association for Cancer Research"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Cancer Research","raw_type":"journal-article"}],"best_oa_location":null,"sustainable_development_goals":[{"display_name":"Good health and well-being","score":0.9537000060081482,"id":"https://metadata.un.org/sdg/3"}],"study_designs":[],"awards":[],"funders":[],"has_content":{"pdf":false,"grobid_xml":false},"content_urls":null,"referenced_works_count":0,"referenced_works":[],"related_works":["https://openalex.org/W7214371547","https://openalex.org/W7148865718","https://openalex.org/W7214315268","https://openalex.org/W4403520045","https://openalex.org/W4323907672","https://openalex.org/W4402551702","https://openalex.org/W7148766024","https://openalex.org/W7163153338","https://openalex.org/W4387245127","https://openalex.org/W4401466831"],"abstract_inverted_index":{"Abstract":[0],"Pancreatic":[1],"ductal":[2,385],"adenocarcinoma":[3,386],"(PDAC)":[4],"is":[5,70,80,179],"an":[6,43,162,238],"aggressive":[7,28],"malignancy":[8],"with":[9,99,176,281,333],"a":[10,155,194,203,214],"5-year":[11],"survival":[12],"rate":[13],"of":[14,26,33,64,96,105,115,129,142,171,185,191,202,226,228,254,266,284,340,355,390],"less":[15],"than":[16],"10%,":[17],"highlighting":[18],"the":[19,34,62,127,183,209,224,264,316,327,352,391],"need":[20],"for":[21,218,318,394],"new":[22],"therapeutic":[23],"options.":[24],"Hallmarks":[25],"this":[27,219],"disease":[29],"include":[30],"constitutive":[31],"activation":[32],"MAPK":[35,135,272,319,378],"signaling":[36,136],"pathway":[37],"via":[38,55,151,346],"mutant":[39],"KRAS":[40,49,65],"(mKRAS)":[41],"and":[42,122,144,173,286,288,306,331],"immunosuppressive":[44],"tumor":[45,68,117],"microenvironment":[46],"(TME).":[47],"Constituently-active":[48],"has":[50],"now":[51],"been":[52],"rendered":[53],"targetable":[54],"clinical-stage":[56],"mKRAS-specific":[57],"small":[58],"molecule":[59],"inhibitors.":[60],"While":[61],"impact":[63],"inhibition":[66,92,150,170,253,283,320,379],"on":[67],"growth":[69],"well-studied,":[71],"its":[72],"ability":[73],"to":[74,134,233,244,299,321,326],"engender":[75],"anti-tumor":[76],"adaptive":[77,328],"immune":[78,329],"responses":[79],"not":[81,207],"fully":[82],"understood.":[83],"Prior":[84],"data":[85,314],"generated":[86],"by":[87,291,343],"our":[88,309],"group":[89],"demonstrated":[90],"mKRAS":[91,147,255,285],"(mKRASi)":[93],"increased":[94,113],"expression":[95,114,141,168,212],"genes":[97],"associated":[98,118],"antigen":[100,130,381],"presentation":[101,131,382],"in":[102,107,132,154,158,165,174,182,193,231,275,308,351,383],"two":[103,116],"models":[104],"PDAC":[106,195,323],"vitro.":[108,159],"Additionally,":[109,337],"proteomic":[110],"analysis":[111],"revealed":[112],"antigens":[119],"(TAAs),":[120],"MSLN":[121,305],"PSCA.":[123],"To":[124,221],"better":[125,222],"understand":[126,223],"alteration":[128,227],"response":[133,232],"perturbation,":[137],"we":[138,236,296],"measured":[139],"surface":[140,167],"MHC-I":[143,166,211,250],"PD-L1":[145],"after":[146,252,263],"and/or":[148,256],"SHP2":[149,172,287],"flow":[152],"cytometry":[153],"PDAC-KRASG12C":[156],"model":[157,197],"Results":[160],"demonstrate":[161],"additive":[163],"increase":[164],"following":[169],"combination":[175],"mKRASi":[177],"that":[178],"more":[180,276,324],"pronounced":[181],"setting":[184],"type":[186,267,292],"I":[187,268,293],"interferon":[188],"(IFN).":[189],"Inhibition":[190],"MEK":[192],"KRASG12D":[196],"recapitulates":[198],"these":[199,234],"findings.":[200],"Addition":[201],"JAK":[204],"inhibitor":[205],"did":[206],"suppress":[208],"additional":[210],"suggesting":[213],"potential":[215,317],"JAK/STAT-independent":[216],"mechanism":[217],"observation.":[220],"extent":[225],"presented":[229,342],"epitopes":[230,278,302,341],"perturbations":[235],"established":[237],"immunopeptidomics":[239],"profiling":[240],"workflow,":[241],"using":[242],"LC-MS/MS":[243],"identify":[245,301],"peptide":[246],"ligands":[247],"eluted":[248],"from":[249,304],"complexes":[251],"SHP2.":[257],"We":[258],"additionally":[259],"profiled":[260],"epitope":[261],"alterations":[262],"addition":[265],"or":[269],"II":[270],"IFN.":[271,294],"perturbation":[273],"resulted":[274],"unique":[277],"identified,":[279],"especially":[280],"dual":[282],"further":[289],"potentiated":[290],"Furthermore,":[295],"were":[297],"able":[298],"directly":[300],"derived":[303],"PSCA":[307],"cell":[310],"line":[311],"models.":[312],"This":[313],"demonstrates":[315],"render":[322],"sensitive":[325],"system":[330],"synergize":[332],"immunotherapeutic":[334],"treatment":[335],"strategies.":[336],"direct":[338],"identification":[339],"cancer":[344],"cells":[345],"mass":[347],"spectrometry":[348],"can":[349],"aid":[350],"rational":[353],"design":[354],"targeted":[356],"immunotherapies.":[357],"Citation":[358],"Format:":[359],"Amanda":[360],"L.":[361],"Creech,":[362],"Thuc":[363],"M.":[364],"Le,":[365],"Evan":[366],"R.":[367,370,373],"Abt,":[368],"Joseph":[369],"Capri,":[371],"Timothy":[372],"Donahue,":[374],"Caius":[375],"G.":[376],"Radu.":[377],"remodels":[380],"pancreatic":[384],"[abstract].":[387],"In:":[388],"Proceedings":[389],"American":[392],"Association":[393],"Cancer":[395,406],"Research":[396],"Annual":[397],"Meeting":[398],"2022;":[399],"2022":[400],"Apr":[401],"8-13.":[402],"Philadelphia":[403],"(PA):":[404],"AACR;":[405],"Res":[407],"2022;82(12_Suppl):Abstract":[408],"nr":[409],"1386.":[410]},"counts_by_year":[{"year":2025,"cited_by_count":1}],"updated_date":"2026-09-22T06:50:58.402377","created_date":"2022-06-17T00:00:00"}