{"id":"https://openalex.org/W4372286240","doi":"https://doi.org/10.1158/2767-9764.c.6604952.v1","title":"Data from p35 is a Crucial Player in NK-cell Cytotoxicity and TGF\u03b2-mediated NK-cell Dysfunction","display_name":"Data from p35 is a Crucial Player in NK-cell Cytotoxicity and TGF\u03b2-mediated NK-cell Dysfunction","publication_year":2023,"publication_date":"2023-05-05","ids":{"openalex":"https://openalex.org/W4372286240","doi":"https://doi.org/10.1158/2767-9764.c.6604952.v1"},"language":"en","primary_location":{"id":"doi:10.1158/2767-9764.c.6604952.v1","doi":"https://doi.org/10.1158/2767-9764.c.6604952.v1","is_oa":true,"landing_page_url":"http://dx.doi.org/10.1158/2767-9764.c.6604952.v1","pdf_url":null,"source":null,"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"American Association for Cancer Research","raw_type":"posted-content"},"volume":null,"type":"other","indexed_in":["crossref"],"open_access":{"is_oa":true,"oa_status":"gold","oa_url":"http://dx.doi.org/10.1158/2767-9764.c.6604952.v1","any_repository_has_fulltext":null},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5086365136","display_name":"Derek P. Wong","orcid":"https://orcid.org/0000-0002-4353-1333","observed_orcids":["https://orcid.org/0000-0002-4353-1333"]},"institutions":[{"id":"https://openalex.org/I58956616","display_name":"Case Western Reserve University","ror":"https://ror.org/051fd9666","country_code":"US","type":"education","lineage":["https://openalex.org/I58956616"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Derek P. Wong","raw_affiliation_strings":["Department of Pathology, Case Western Reserve University, Cleveland, OH, USA"],"raw_orcid":"https://orcid.org/0000-0002-4353-1333","affiliations":[{"raw_affiliation_string":"Department of Pathology, Case Western Reserve University, Cleveland, OH, USA","institution_ids":["https://openalex.org/I58956616"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5017253021","display_name":"Claire E. Fritz","orcid":"https://orcid.org/0000-0001-7074-2323","observed_orcids":["https://orcid.org/0000-0001-7074-2323"]},"institutions":[{"id":"https://openalex.org/I58956616","display_name":"Case Western Reserve University","ror":"https://ror.org/051fd9666","country_code":"US","type":"education","lineage":["https://openalex.org/I58956616"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Claire E. Fritz","raw_affiliation_strings":["Department of Pathology, Case Western Reserve University, Cleveland, OH, USA"],"raw_orcid":"https://orcid.org/0000-0001-7074-2323","affiliations":[{"raw_affiliation_string":"Department of Pathology, Case Western Reserve University, Cleveland, OH, USA","institution_ids":["https://openalex.org/I58956616"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5074314576","display_name":"Daniel M. Feinberg","orcid":"https://orcid.org/0000-0003-4833-6470","observed_orcids":["https://orcid.org/0000-0003-4833-6470"]},"institutions":[{"id":"https://openalex.org/I58956616","display_name":"Case Western Reserve University","ror":"https://ror.org/051fd9666","country_code":"US","type":"education","lineage":["https://openalex.org/I58956616"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Daniel Feinberg","raw_affiliation_strings":["Department of Pathology, Case Western Reserve University, Cleveland, OH, USA"],"raw_orcid":"https://orcid.org/0000-0003-4833-6470","affiliations":[{"raw_affiliation_string":"Department of Pathology, Case Western Reserve University, Cleveland, OH, USA","institution_ids":["https://openalex.org/I58956616"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5025536959","display_name":"Alex Yee-Chen Huang","orcid":"https://orcid.org/0000-0002-5701-4521","observed_orcids":["https://orcid.org/0000-0002-5701-4521"]},"institutions":[{"id":"https://openalex.org/I4210151235","display_name":"Rainbow Babies & Children's Hospital","ror":"https://ror.org/04x495f64","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I2799343972","https://openalex.org/I4210151235"]},{"id":"https://openalex.org/I4390039247","display_name":"Case Comprehensive Cancer Center","ror":"https://ror.org/00fpjq451","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I4390039247","https://openalex.org/I58956616"]},{"id":"https://openalex.org/I58956616","display_name":"Case Western Reserve University","ror":"https://ror.org/051fd9666","country_code":"US","type":"education","lineage":["https://openalex.org/I58956616"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Alex Y. Huang","raw_affiliation_strings":["Pediatric Hematology and Oncology, The Angie Fowler Adolescent & Young Adult Cancer Institute, University Hospitals Rainbow Babies & Children's Hospital, Cleveland, OH, USA","The Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, OH, USA"],"raw_orcid":"https://orcid.org/0000-0002-5701-4521","affiliations":[{"raw_affiliation_string":"Pediatric Hematology and Oncology, The Angie Fowler Adolescent & Young Adult Cancer Institute, University Hospitals Rainbow Babies & Children's Hospital, Cleveland, OH, USA","institution_ids":["https://openalex.org/I4210151235"]},{"raw_affiliation_string":"The Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, OH, USA","institution_ids":["https://openalex.org/I4390039247","https://openalex.org/I58956616"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5085253443","display_name":"Reshmi Parameswaran","orcid":"https://orcid.org/0000-0002-8043-7450","observed_orcids":["https://orcid.org/0000-0002-8043-7450"]},"institutions":[{"id":"https://openalex.org/I4390039247","display_name":"Case Comprehensive Cancer Center","ror":"https://ror.org/00fpjq451","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I4390039247","https://openalex.org/I58956616"]},{"id":"https://openalex.org/I58956616","display_name":"Case Western Reserve University","ror":"https://ror.org/051fd9666","country_code":"US","type":"education","lineage":["https://openalex.org/I58956616"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Reshmi Parameswaran","raw_affiliation_strings":["Division of Hematology/Oncology, Department of Medicine, Case Western Reserve University, Cleveland, OH, USA","The Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, OH, USA"],"raw_orcid":"https://orcid.org/0000-0002-8043-7450","affiliations":[{"raw_affiliation_string":"Division of Hematology/Oncology, Department of Medicine, Case Western Reserve University, Cleveland, OH, USA","institution_ids":["https://openalex.org/I58956616"]},{"raw_affiliation_string":"The Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, OH, USA","institution_ids":["https://openalex.org/I4390039247","https://openalex.org/I58956616"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":3,"corresponding_author_ids":[],"corresponding_institution_ids":[],"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":null,"last_page":null},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T11020","display_name":"Immune Cell Function and Interaction","score":1.0,"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"}},"topics":[{"id":"https://openalex.org/T11020","display_name":"Immune Cell Function and Interaction","score":1.0,"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/T11313","display_name":"Immune cells in cancer","score":0.0,"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/T10031","display_name":"T-cell and B-cell Immunology","score":0.0,"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/p35","display_name":"p35","score":0.9459999799728394},{"id":"https://openalex.org/keywords/cdk5r1","display_name":"CDK5R1","score":0.9340000152587891},{"id":"https://openalex.org/keywords/cdk5","display_name":"cyclin-dependent kinase 5","score":0.9070000052452087},{"id":"https://openalex.org/keywords/natural-killer-cells","display_name":"natural killer cells","score":0.9319999814033508},{"id":"https://openalex.org/keywords/nk-cell-cytotoxicity","display_name":"NK cell cytotoxicity","score":0.996999979019165},{"id":"https://openalex.org/keywords/transforming-growth-factor-beta","display_name":"TGF-beta","score":0.8880000114440918},{"id":"https://openalex.org/keywords/nk-cell-exhaustion","display_name":"NK cell exhaustion","score":0.9559999704360962},{"id":"https://openalex.org/keywords/adoptive-nk-cell-therapy","display_name":"adoptive NK cell therapy","score":0.8140000104904175},{"id":"https://openalex.org/keywords/kinase-activity","display_name":"kinase activity","score":0.5979999899864197},{"id":"https://openalex.org/keywords/tumor-cell-killing","display_name":"tumor cell killing","score":0.6179999709129333}],"concepts":[{"id":"https://openalex.org/C109316439","wikidata":"https://www.wikidata.org/wiki/Q246181","display_name":"Cytotoxicity","level":3,"score":0.8293864727020264},{"id":"https://openalex.org/C28651165","wikidata":"https://www.wikidata.org/wiki/Q4259786","display_name":"Lymphokine-activated killer cell","level":5,"score":0.5742233991622925},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.5465866327285767},{"id":"https://openalex.org/C95444343","wikidata":"https://www.wikidata.org/wiki/Q7141","display_name":"Cell biology","level":1,"score":0.5110045671463013},{"id":"https://openalex.org/C154317977","wikidata":"https://www.wikidata.org/wiki/Q376266","display_name":"Cytotoxic T cell","level":3,"score":0.5090362429618835},{"id":"https://openalex.org/C190232843","wikidata":"https://www.wikidata.org/wiki/Q1950808","display_name":"Small hairpin RNA","level":4,"score":0.4920320212841034},{"id":"https://openalex.org/C2778102761","wikidata":"https://www.wikidata.org/wiki/Q332181","display_name":"Natural killer cell","level":4,"score":0.4739168584346771},{"id":"https://openalex.org/C1491633281","wikidata":"https://www.wikidata.org/wiki/Q7868","display_name":"Cell","level":2,"score":0.45550063252449036},{"id":"https://openalex.org/C183315844","wikidata":"https://www.wikidata.org/wiki/Q6155969","display_name":"Janus kinase 3","level":5,"score":0.45212864875793457},{"id":"https://openalex.org/C129374314","wikidata":"https://www.wikidata.org/wiki/Q909381","display_name":"Interleukin 21","level":4,"score":0.4371492266654968},{"id":"https://openalex.org/C502942594","wikidata":"https://www.wikidata.org/wiki/Q3421914","display_name":"Cancer research","level":1,"score":0.3946729302406311},{"id":"https://openalex.org/C190283241","wikidata":"https://www.wikidata.org/wiki/Q14599311","display_name":"Apoptosis","level":2,"score":0.3362904191017151},{"id":"https://openalex.org/C202751555","wikidata":"https://www.wikidata.org/wiki/Q221681","display_name":"In vitro","level":2,"score":0.12221083045005798},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.103782057762146},{"id":"https://openalex.org/C173396325","wikidata":"https://www.wikidata.org/wiki/Q1501275","display_name":"Gene knockdown","level":3,"score":0.081301748752594}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.1158/2767-9764.c.6604952.v1","doi":"https://doi.org/10.1158/2767-9764.c.6604952.v1","is_oa":true,"landing_page_url":"http://dx.doi.org/10.1158/2767-9764.c.6604952.v1","pdf_url":null,"source":null,"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"American Association for Cancer Research","raw_type":"posted-content"}],"best_oa_location":{"id":"doi:10.1158/2767-9764.c.6604952.v1","doi":"https://doi.org/10.1158/2767-9764.c.6604952.v1","is_oa":true,"landing_page_url":"http://dx.doi.org/10.1158/2767-9764.c.6604952.v1","pdf_url":null,"source":null,"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"American Association for Cancer Research","raw_type":"posted-content"},"sustainable_development_goals":[{"id":"https://metadata.un.org/sdg/3","score":0.9763000011444092,"display_name":"Good health and well-being"}],"study_designs":[],"awards":[{"id":"https://openalex.org/G1273157147","display_name":null,"funder_award_id":"P30 CA043703","funder_id":"https://openalex.org/F4320310595","funder_display_name":"Case Comprehensive Cancer Center, Case Western Reserve University"},{"id":"https://openalex.org/G9000862237","display_name":"Case Comprehensive Cancer Center Support Grant","funder_award_id":"P30CA043703","funder_id":"https://openalex.org/F4320337351","funder_display_name":"National Cancer Institute"}],"funders":[{"id":"https://openalex.org/F4320310281","display_name":"Case Western Reserve University","ror":"https://ror.org/051fd9666"},{"id":"https://openalex.org/F4320310595","display_name":"Case Comprehensive Cancer Center, Case Western Reserve University","ror":"https://ror.org/051fd9666"},{"id":"https://openalex.org/F4320337351","display_name":"National Cancer Institute","ror":"https://ror.org/040gcmg81"}],"has_content":{"grobid_xml":false,"pdf":false},"content_urls":null,"referenced_works_count":45,"referenced_works":["https://openalex.org/W1039448529","https://openalex.org/W1571796034","https://openalex.org/W1577397450","https://openalex.org/W1772986380","https://openalex.org/W1964830067","https://openalex.org/W1971468364","https://openalex.org/W2005755208","https://openalex.org/W2009204794","https://openalex.org/W2009342562","https://openalex.org/W2012195301","https://openalex.org/W2016311545","https://openalex.org/W2028559822","https://openalex.org/W2042437382","https://openalex.org/W2046640720","https://openalex.org/W2058182256","https://openalex.org/W2064351015","https://openalex.org/W2068180488","https://openalex.org/W2089465156","https://openalex.org/W2091675007","https://openalex.org/W2098921291","https://openalex.org/W2108318095","https://openalex.org/W2118447882","https://openalex.org/W2130229338","https://openalex.org/W2132503351","https://openalex.org/W2135118850","https://openalex.org/W2162704072","https://openalex.org/W2178222994","https://openalex.org/W2211008635","https://openalex.org/W2221432805","https://openalex.org/W2287383446","https://openalex.org/W2502908858","https://openalex.org/W2529684147","https://openalex.org/W2582546017","https://openalex.org/W2595955064","https://openalex.org/W2618174085","https://openalex.org/W2756061744","https://openalex.org/W2776314135","https://openalex.org/W2785341808","https://openalex.org/W2802860523","https://openalex.org/W2924459278","https://openalex.org/W2944519468","https://openalex.org/W2949364722","https://openalex.org/W2973102008","https://openalex.org/W2999846808","https://openalex.org/W4287307650"],"related_works":["https://openalex.org/W4366338968","https://openalex.org/W4313422850","https://openalex.org/W4372286242","https://openalex.org/W4372184667","https://openalex.org/W4372286362","https://openalex.org/W4372286237","https://openalex.org/W4372286360","https://openalex.org/W4399325226","https://openalex.org/W6910311457","https://openalex.org/W2051546748"],"abstract_inverted_index":{"Natural":[0],"killer":[1],"(NK)":[2],"cells":[3,71,76,111,133,179,188],"are":[4,54,67,73],"innate":[5],"lymphocytes":[6],"with":[7,113,181,190],"cytotoxic":[8],"activity.":[9],"Understanding":[10],"the":[11,50],"factors":[12],"regulating":[13],"cytotoxicity":[14,87,123,229],"is":[15],"crucial":[16],"for":[17,225],"improving":[18],"NK-cell":[19,40,158,170,217,228,236],"adoptive":[20,237],"therapies.":[21],"Here,":[22,60],"we":[23,61,161],"studied":[24],"a":[25,32,142,165,223],"previously":[26],"unknown":[27],"role":[28,214,224],"of":[29,34,52,129,145,169,200],"p35":[30,42,66,78,114,130,155,173,191,210,226],"(CDK5R1),":[31],"coactivator":[33],"cyclin-dependent":[35],"kinase":[36],"5":[37],"(CDK5)":[38],"in":[39,69,99,122,131,135,138,175,215,227],"function.":[41],"expression":[43,174,196],"was":[44],"thought":[45],"to":[46,205,234],"be":[47],"neuronal-specific":[48],"and":[49,65,72,83,230],"majority":[51],"studies":[53],"still":[55],"focused":[56],"on":[57],"neuronal":[58],"cells.":[59,127,177],"show":[62,96],"that":[63,154,163,209],"CDK5":[64,146,195],"expressed":[68],"NK":[70,75,110,132,176,178,187],"kinase-active.":[74],"from":[77],"knockout":[79],"mice":[80],"were":[81],"analyzed":[82],"showed":[84],"significantly":[85],"increased":[86,148],"against":[88,124],"murine":[89],"cancer":[90,126],"cells,":[91],"while":[92,140,186],"they":[93],"did":[94],"not":[95],"any":[97],"differences":[98],"cell":[100],"numbers":[101],"or":[102,193],"maturation":[103],"stages.":[104],"We":[105],"confirmed":[106],"this":[107,201,231],"using":[108],"human":[109,125],"transduced":[112,189],"short":[115],"hairpin":[116],"RNA":[117],"(shRNA),":[118],"showing":[119],"similar":[120],"increase":[121],"Overexpression":[128],"resulted":[134],"moderate":[136],"decrease":[137],"cytotoxicity,":[139,171,185],"expressing":[141],"kinase-dead":[143],"mutant":[144,194],"displayed":[147],"cytotoxicity.":[149,159],"Together,":[150],"these":[151],"data":[152],"suggest":[153],"negatively":[156],"regulates":[157],"Surprisingly,":[160],"found":[162],"TGF\u03b2,":[164],"known":[166],"negative":[167],"regulator":[168],"induces":[172],"cultured":[180],"TGF\u03b2":[182],"exhibit":[183],"reduced":[184],"shRNA":[192],"exhibited":[197],"partial":[198],"reversal":[199],"inhibitory":[202],"effect":[203],"pointing":[204],"an":[206,212],"interesting":[207],"hypothesis":[208],"plays":[211],"important":[213],"TGF\u03b2-mediated":[216],"exhaustion.":[218],"Significance:":[219],"This":[220],"study":[221],"reports":[222],"might":[232],"help":[233],"improve":[235],"therapy.":[238]},"counts_by_year":[],"updated_date":"2026-10-27T15:51:10.671819","created_date":"2023-05-07T00:00:00"}
