{"id":"https://openalex.org/W4241031437","doi":"https://doi.org/10.1158/1538-7445.sabcs18-4723","title":"Abstract 4723: Combinatorial efficacy of anti-PD1 treatment and selective histone deacetylase 6 (HDAC6) inhibition in chronic lymphocytic leukemia (CLL)","display_name":"Abstract 4723: Combinatorial efficacy of anti-PD1 treatment and selective histone deacetylase 6 (HDAC6) inhibition in chronic lymphocytic leukemia (CLL)","publication_year":2019,"publication_date":"2019-07-01","ids":{"openalex":"https://openalex.org/W4241031437","doi":"https://doi.org/10.1158/1538-7445.sabcs18-4723"},"language":"en","primary_location":{"id":"doi:10.1158/1538-7445.sabcs18-4723","doi":"https://doi.org/10.1158/1538-7445.sabcs18-4723","is_oa":false,"landing_page_url":"https://doi.org/10.1158/1538-7445.sabcs18-4723","pdf_url":null,"source":{"id":"https://openalex.org/S4306510252","display_name":"Experimental and Molecular Therapeutics","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":null,"host_organization_name":null,"host_organization_lineage":[],"host_organization_lineage_names":[],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Experimental and Molecular Therapeutics","raw_type":"proceedings-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/A5045207617","display_name":"Kamira Karen Maharaj","orcid":"https://orcid.org/0000-0002-2721-1188","observed_orcids":["https://orcid.org/0000-0002-2721-1188"]},"institutions":[{"id":"https://openalex.org/I3019308854","display_name":"Moffitt Cancer Center","ror":"https://ror.org/01xf75524","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I3019308854"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Kamira Maharaj","raw_affiliation_strings":["H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL","institution_ids":["https://openalex.org/I3019308854"]}]},{"author_position":"middle","author":{"id":null,"display_name":"John Powers","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I3019308854","display_name":"Moffitt Cancer Center","ror":"https://ror.org/01xf75524","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I3019308854"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"John Powers","raw_affiliation_strings":["H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL","institution_ids":["https://openalex.org/I3019308854"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5045125844","display_name":"Alex N. Achille","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I3019308854","display_name":"Moffitt Cancer Center","ror":"https://ror.org/01xf75524","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I3019308854"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Alex Achille","raw_affiliation_strings":["H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL","institution_ids":["https://openalex.org/I3019308854"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5085814876","display_name":"Eva Sahakian","orcid":"https://orcid.org/0000-0001-6930-2275","observed_orcids":["https://orcid.org/0000-0001-6930-2275"]},"institutions":[{"id":"https://openalex.org/I3019308854","display_name":"Moffitt Cancer Center","ror":"https://ror.org/01xf75524","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I3019308854"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Eva Sahakian","raw_affiliation_strings":["H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL","institution_ids":["https://openalex.org/I3019308854"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5101811382","display_name":"Javier A. Pinilla-Ibarz","orcid":"https://orcid.org/0000-0003-3170-9648","observed_orcids":["https://orcid.org/0000-0003-3170-9648"]},"institutions":[{"id":"https://openalex.org/I3019308854","display_name":"Moffitt Cancer Center","ror":"https://ror.org/01xf75524","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I3019308854"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Javier Pinilla-Ibarz","raw_affiliation_strings":["H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL","institution_ids":["https://openalex.org/I3019308854"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"corresponding_author_ids":[],"corresponding_institution_ids":["https://openalex.org/I3019308854"],"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":null,"issue":null,"first_page":"4723","last_page":"4723"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T11157","display_name":"Chronic Lymphocytic Leukemia Research","score":0.9990000128746033,"subfield":{"id":"https://openalex.org/subfields/2716","display_name":"Genetics (clinical)"},"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/T11157","display_name":"Chronic Lymphocytic Leukemia Research","score":0.9990000128746033,"subfield":{"id":"https://openalex.org/subfields/2716","display_name":"Genetics (clinical)"},"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/T11736","display_name":"Histone Deacetylase Inhibitors Research","score":0.0003000000142492354,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T10185","display_name":"Lymphoma Diagnosis and Treatment","score":9.999999747378752e-05,"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/chronic-lymphocytic-leukemia","display_name":"chronic lymphocytic leukemia","score":0.9860000014305115},{"id":"https://openalex.org/keywords/hdac6-inhibition","display_name":"HDAC6 inhibition","score":0.8999999761581421},{"id":"https://openalex.org/keywords/anti-pd-1-therapy","display_name":"anti-PD-1 therapy","score":0.953000009059906},{"id":"https://openalex.org/keywords/combination-immunotherapy","display_name":"combination immunotherapy","score":0.722000002861023},{"id":"https://openalex.org/keywords/tumor-immunosuppression","display_name":"tumor immunosuppression","score":0.828000009059906},{"id":"https://openalex.org/keywords/pd-l1","display_name":"PD-L1","score":0.8080000281333923},{"id":"https://openalex.org/keywords/il-10","display_name":"IL-10","score":0.9760000109672546},{"id":"https://openalex.org/keywords/t-cell-exhaustion","display_name":"T cell exhaustion","score":0.7620000243186951},{"id":"https://openalex.org/keywords/regulatory-t-cells","display_name":"regulatory T cells","score":0.8140000104904175},{"id":"https://openalex.org/keywords/tumor-associated-macrophages","display_name":"tumor-associated macrophages","score":0.6449999809265137},{"id":"https://openalex.org/keywords/m2-macrophage-polarization","display_name":"M2 macrophage polarization","score":0.6230000257492065},{"id":"https://openalex.org/keywords/tumor-microenvironment","display_name":"tumor microenvironment","score":0.5460000038146973},{"id":"https://openalex.org/keywords/adoptive-transfer-model","display_name":"adoptive transfer model","score":0.5239999890327454}],"concepts":[{"id":"https://openalex.org/C23681527","wikidata":"https://www.wikidata.org/wiki/Q18034953","display_name":"HDAC6","level":5,"score":0.8373497128486633},{"id":"https://openalex.org/C2777938653","wikidata":"https://www.wikidata.org/wiki/Q1088156","display_name":"Chronic lymphocytic leukemia","level":3,"score":0.836959719657898},{"id":"https://openalex.org/C502942594","wikidata":"https://www.wikidata.org/wiki/Q3421914","display_name":"Cancer research","level":1,"score":0.5413093566894531},{"id":"https://openalex.org/C2778305200","wikidata":"https://www.wikidata.org/wiki/Q174378","display_name":"Histone deacetylase","level":4,"score":0.5017974376678467},{"id":"https://openalex.org/C2778461978","wikidata":"https://www.wikidata.org/wiki/Q29496","display_name":"Leukemia","level":2,"score":0.462873250246048},{"id":"https://openalex.org/C64927066","wikidata":"https://www.wikidata.org/wiki/Q36293","display_name":"Histone","level":3,"score":0.456390380859375},{"id":"https://openalex.org/C142354902","wikidata":"https://www.wikidata.org/wiki/Q18047334","display_name":"HDAC10","level":5,"score":0.4323870539665222},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.3887621760368347},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.36714088916778564},{"id":"https://openalex.org/C126322002","wikidata":"https://www.wikidata.org/wiki/Q11180","display_name":"Internal medicine","level":1,"score":0.24949923157691956},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.17789047956466675},{"id":"https://openalex.org/C104317684","wikidata":"https://www.wikidata.org/wiki/Q7187","display_name":"Gene","level":2,"score":0.08764833211898804}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.1158/1538-7445.sabcs18-4723","doi":"https://doi.org/10.1158/1538-7445.sabcs18-4723","is_oa":false,"landing_page_url":"https://doi.org/10.1158/1538-7445.sabcs18-4723","pdf_url":null,"source":{"id":"https://openalex.org/S4306510252","display_name":"Experimental and Molecular Therapeutics","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":null,"host_organization_name":null,"host_organization_lineage":[],"host_organization_lineage_names":[],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Experimental and Molecular Therapeutics","raw_type":"proceedings-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/W2492326185","https://openalex.org/W2588078525","https://openalex.org/W3108746969","https://openalex.org/W2901494388","https://openalex.org/W3112211877","https://openalex.org/W2743624206","https://openalex.org/W2499353596","https://openalex.org/W4282958632","https://openalex.org/W2487527462","https://openalex.org/W2338701266"],"abstract_inverted_index":{"A":[0],"suppressive":[1],"microenvironment":[2],"allows":[3],"CLL":[4,28,102,120,139,154,168,191,218,228,326,355,370,381,416],"B":[5,103,224,237,281,305,310,335],"cells":[6,104,225,238,264,282,306,356],"to":[7,23,32,58,108,130,227,308,358,406],"avoid":[8],"immune":[9,17,25,73,140,413],"surveillance.":[10],"Coinhibitory":[11],"antigens,":[12],"anti-inflammatory":[13],"cytokines":[14],"and":[15,21,50,74,86,95,105,142,161,210,243,249,257,270,289,348,384,411,434],"skewed":[16],"populations":[18],"support":[19],"malignancy":[20],"contribute":[22],"poorer":[24],"responses":[26],"in":[27,48,64,93,119,177,217,230,365,393,415,441],"patients.":[29],"Novel":[30],"approaches":[31],"counter":[33],"immunosuppression":[34,118],"are":[35],"therefore":[36],"being":[37],"explored.":[38],"The":[39,124],"HDAC":[40],"family":[41],"of":[42,62,72,126,135,151,166,241,274,346,354,386,431,449],"proteins":[43],"epigenetically":[44],"regulate":[45],"immune-related":[46],"pathways":[47],"cancer":[49],"may":[51,68],"be":[52,318,320,403],"noteworthy":[53],"immunomodulatory":[54],"targets.":[55],"In":[56,246,372],"addition":[57],"the":[59,133,159,352,450],"recognized":[60],"role":[61],"HDACs":[63],"cell":[65,91,295],"survival,":[66],"HDACi":[67],"alter":[69],"inflammatory":[70],"status":[71],"tumor":[75,409],"cells.":[76,261,293,311],"We":[77,312],"have":[78],"previously":[79],"reported":[80],"that":[81,114,315,338,377,399],"HDAC6":[82],"regulates":[83],"IL-10":[84,98],"transcription,":[85],"is":[87,99,106],"responsible":[88],"for":[89,121,153,325,453],"T":[90,219,260,263,292,294,382],"anergy":[92],"murine":[94,167],"human":[96],"APCs.":[97],"secreted":[100],"by":[101],"thought":[107],"influence":[109],"immunosuppression.":[110],"Therefore,":[111],"we":[112,374],"hypothesized":[113,314],"HDAC6i":[115,137,147,378,387],"could":[116,148,317,402],"reverse":[117],"antitumor":[122],"benefit.":[123,343],"purpose":[125],"this":[127,400],"study":[128],"was":[129,174,183,251,299],"determine":[131],"1)":[132],"effects":[134],"selective":[136,435],"on":[138,223,253],"biology":[141],"2)":[143],"whether":[144],"combination":[145,345,385,401],"with":[146,287,291,303,322,330,388],"improve":[149,412],"efficacy":[150,392,430],"anti-PD1":[152,323,331,349,363,389,432],"therapy.To":[155],"accomplish":[156],"these":[157],"aims,":[158],"euTCL1":[160,231,236,280],"euTCL1/HDAC6KO":[162,366],"adoptive":[163],"transfer":[164],"models":[165],"were":[169,194,203,213,283],"utilized.":[170],"ACY738":[171,234,266,288,316,347],"(selective":[172],"HDAC6i)":[173],"administered":[175,184],"orally":[176],"chow":[178],"at":[179,189],"25mpk":[180],"daily.":[181],"Anti-PD1":[182],"intraperitoneally":[185],"3x":[186],"per":[187],"week":[188],"3mpk.":[190],"surface":[192],"antigens":[193],"analyzed":[195],"via":[196,215],"flow":[197],"cytometry.":[198],"Functional":[199],"mixed":[200],"lymphocyte":[201],"assays":[202],"performed":[204],"ex":[205,285],"vivo,":[206],"measuring":[207],"IFNg":[208],"production,":[209],"Th1/Th2":[211],"factors":[212],"examined":[214],"qRT-PCR":[216],"cells.Early":[220],"PD-L1":[221,242],"expression":[222,240],"correlated":[226],"burden":[229,410],"mice.":[232],"Post":[233],"treatment,":[235],"downregulated":[239,271],"plasma":[244],"IL-10.":[245],"addition,":[247],"PD-1":[248],"CTLA4":[250],"decreased":[252],"CD4+,":[254],"CD8+,":[255],"Tregs":[256],"effector":[258],"memory":[259],"Splenic":[262],"from":[265],"mice":[267,367],"upregulated":[268],"TBET":[269],"GATA3,":[272],"indicative":[273],"a":[275],"less":[276],"exhausted":[277],"phenotype.":[278],"Subsequently,":[279],"treated":[284,304,329],"vivo":[286],"cocultured":[290],"activation":[296],"(IFNg":[297],"production)":[298],"increased":[300,390],"after":[301],"coculture":[302],"compared":[307,357],"control":[309],"then":[313],"rationally":[319],"combined":[321],"mAb":[324],"treatment.":[327],"Mice":[328],"accumulated":[332],"fewer":[333],"CD5+":[334],"cells,":[336,383],"confirming":[337],"PD-1/PD-L1":[339],"blockade":[340],"demonstrated":[341],"anti-CLL":[342,391],"Strikingly,":[344],"further":[350,368],"delayed":[351,369],"growth":[353],"either":[359],"single":[360],"agent.":[361],"Consistently,":[362],"treatment":[364,433],"development.":[371],"conclusion,":[373],"report":[375],"here":[376],"can":[379],"reinvigorate":[380],"vivo.":[394],"This":[395],"work":[396],"provides":[397],"evidence":[398],"clinically":[404],"investigated":[405],"simultaneously":[407],"reduce":[408],"function":[414],"patients.Citation":[417],"Format:":[418],"Kamira":[419],"Maharaj,":[420],"John":[421],"Powers,":[422],"Alex":[423],"Achille,":[424],"Eva":[425],"Sahakian,":[426],"Javier":[427],"Pinilla-Ibarz.":[428],"Combinatorial":[429],"histone":[436],"deacetylase":[437],"6":[438],"(HDAC6)":[439],"inhibition":[440],"chronic":[442],"lymphocytic":[443],"leukemia":[444],"(CLL)":[445],"[abstract].":[446],"In:":[447],"Proceedings":[448],"American":[451],"Association":[452],"Cancer":[454,468],"Research":[455],"Annual":[456],"Meeting":[457],"2019;":[458],"2019":[459],"Mar":[460],"29-Apr":[461],"3;":[462],"Atlanta,":[463],"GA.":[464],"Philadelphia":[465],"(PA):":[466],"AACR;":[467],"Res":[469],"2019;79(13":[470],"Suppl):Abstract":[471],"nr":[472],"4723.":[473]},"counts_by_year":[],"updated_date":"2026-11-04T10:54:05.112534","created_date":"2022-05-12T00:00:00"}
