{"id":"https://openalex.org/W4310125637","doi":"https://doi.org/10.1182/blood-2022-169006","title":"Characterization of a Cyclic Dinucleotide Metabolic Switch to Fuel Antitumor Immunity","display_name":"Characterization of a Cyclic Dinucleotide Metabolic Switch to Fuel Antitumor Immunity","publication_year":2022,"publication_date":"2022-11-15","ids":{"openalex":"https://openalex.org/W4310125637","doi":"https://doi.org/10.1182/blood-2022-169006"},"language":"en","primary_location":{"id":"doi:10.1182/blood-2022-169006","doi":"https://doi.org/10.1182/blood-2022-169006","is_oa":false,"landing_page_url":"https://doi.org/10.1182/blood-2022-169006","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":"article","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/A5039584806","display_name":"Jeremy A. Meier","orcid":"https://orcid.org/0000-0001-6321-5971","observed_orcids":["https://orcid.org/0000-0001-6321-5971"]},"institutions":[{"id":"https://openalex.org/I114027177","display_name":"University of North Carolina at Chapel Hill","ror":"https://ror.org/0130frc33","country_code":"US","type":"education","lineage":["https://openalex.org/I114027177"]},{"id":"https://openalex.org/I4390039329","display_name":"UNC Lineberger Comprehensive Cancer Center","ror":"https://ror.org/043ehm030","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I114027177","https://openalex.org/I4390039329"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Jeremy A. Meier","raw_affiliation_strings":["1Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC","2Department of Medicine, Division of Hematology, University of North Carolina, Chapel Hill, NC"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC","institution_ids":["https://openalex.org/I114027177","https://openalex.org/I4390039329"]},{"raw_affiliation_string":"2Department of Medicine, Division of Hematology, University of North Carolina, Chapel Hill, NC","institution_ids":["https://openalex.org/I114027177"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5004671421","display_name":"Katie E. Hurst","orcid":"https://orcid.org/0000-0003-4744-4971","observed_orcids":["https://orcid.org/0000-0003-4744-4971","https://orcid.org/0000-0002-6878-5727"]},"institutions":[{"id":"https://openalex.org/I114027177","display_name":"University of North Carolina at Chapel Hill","ror":"https://ror.org/0130frc33","country_code":"US","type":"education","lineage":["https://openalex.org/I114027177"]},{"id":"https://openalex.org/I4390039329","display_name":"UNC Lineberger Comprehensive Cancer Center","ror":"https://ror.org/043ehm030","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I114027177","https://openalex.org/I4390039329"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Katie E. Hurst","raw_affiliation_strings":["1Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC","3Department of Cell Biology and Physiology, University of North Carolina, Chapel Hill, NC"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC","institution_ids":["https://openalex.org/I114027177","https://openalex.org/I4390039329"]},{"raw_affiliation_string":"3Department of Cell Biology and Physiology, University of North Carolina, Chapel Hill, NC","institution_ids":["https://openalex.org/I114027177"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5058546269","display_name":"David L. Corcoran","orcid":"https://orcid.org/0000-0001-7460-9247","observed_orcids":["https://orcid.org/0000-0001-7460-9247"]},"institutions":[{"id":"https://openalex.org/I114027177","display_name":"University of North Carolina at Chapel Hill","ror":"https://ror.org/0130frc33","country_code":"US","type":"education","lineage":["https://openalex.org/I114027177"]},{"id":"https://openalex.org/I4390039329","display_name":"UNC Lineberger Comprehensive Cancer Center","ror":"https://ror.org/043ehm030","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I114027177","https://openalex.org/I4390039329"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"David L. Corcoran","raw_affiliation_strings":["1Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC","4Department of Genetics, University of North Carolina, Chapel Hill, NC"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC","institution_ids":["https://openalex.org/I114027177","https://openalex.org/I4390039329"]},{"raw_affiliation_string":"4Department of Genetics, University of North Carolina, Chapel Hill, NC","institution_ids":["https://openalex.org/I114027177"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5091728889","display_name":"Jessica E. Thaxton","orcid":"https://orcid.org/0000-0003-1759-5576","observed_orcids":["https://orcid.org/0000-0003-1759-5576"]},"institutions":[{"id":"https://openalex.org/I114027177","display_name":"University of North Carolina at Chapel Hill","ror":"https://ror.org/0130frc33","country_code":"US","type":"education","lineage":["https://openalex.org/I114027177"]},{"id":"https://openalex.org/I4390039329","display_name":"UNC Lineberger Comprehensive Cancer Center","ror":"https://ror.org/043ehm030","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I114027177","https://openalex.org/I4390039329"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Jessica E. Thaxton","raw_affiliation_strings":["1Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC","3Department of Cell Biology and Physiology, University of North Carolina, Chapel Hill, NC"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"1Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC","institution_ids":["https://openalex.org/I114027177","https://openalex.org/I4390039329"]},{"raw_affiliation_string":"3Department of Cell Biology and Physiology, University of North Carolina, Chapel Hill, NC","institution_ids":["https://openalex.org/I114027177"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5026510629","display_name":"Jonathan Stuart Serody","orcid":"https://orcid.org/0000-0003-4568-1092","observed_orcids":["https://orcid.org/0000-0003-4568-1092"]},"institutions":[{"id":"https://openalex.org/I114027177","display_name":"University of North Carolina at Chapel Hill","ror":"https://ror.org/0130frc33","country_code":"US","type":"education","lineage":["https://openalex.org/I114027177"]},{"id":"https://openalex.org/I4390039329","display_name":"UNC Lineberger Comprehensive Cancer Center","ror":"https://ror.org/043ehm030","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I114027177","https://openalex.org/I4390039329"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Jonathan S. Serody","raw_affiliation_strings":["2Department of Medicine, Division of Hematology, University of North Carolina, Chapel Hill, NC","5Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC","6Department of Microbiology & Immunology, University of North Carolina, Chapel Hill, NC"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"2Department of Medicine, Division of Hematology, University of North Carolina, Chapel Hill, NC","institution_ids":["https://openalex.org/I114027177"]},{"raw_affiliation_string":"5Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC","institution_ids":["https://openalex.org/I114027177","https://openalex.org/I4390039329"]},{"raw_affiliation_string":"6Department of Microbiology & Immunology, University of North Carolina, Chapel Hill, NC","institution_ids":["https://openalex.org/I114027177"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":2,"corresponding_author_ids":[],"corresponding_institution_ids":[],"apc_list":{"value":2500,"currency":"USD","value_usd":2500},"apc_paid":null,"fwci":0.0,"has_fulltext":false,"cited_by_count":0,"citation_normalized_percentile":{"value":0.19458969,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":null,"biblio":{"volume":"140","issue":"Supplement 1","first_page":"4526","last_page":"4527"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T11491","display_name":"CAR-T cell therapy research","score":0.5386000275611877,"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/T11491","display_name":"CAR-T cell therapy research","score":0.5386000275611877,"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":0.10649999976158142,"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":0.1014999970793724,"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/cgamp","display_name":"cGAMP","score":0.7419999837875366},{"id":"https://openalex.org/keywords/cyclic-dinucleotides","display_name":"cyclic dinucleotides","score":0.9670000076293945},{"id":"https://openalex.org/keywords/chimeric-antigen-receptor-t-cells","display_name":"chimeric antigen receptor T cells","score":0.8240000009536743},{"id":"https://openalex.org/keywords/t-cell-metabolism","display_name":"T cell metabolism","score":0.8790000081062317},{"id":"https://openalex.org/keywords/fatty-acid-oxidation","display_name":"fatty acid oxidation","score":0.824999988079071},{"id":"https://openalex.org/keywords/t-cell-exhaustion","display_name":"T cell exhaustion","score":0.6729999780654907},{"id":"https://openalex.org/keywords/tcf1","display_name":"TCF1","score":0.550000011920929},{"id":"https://openalex.org/keywords/lef1","display_name":"LEF1","score":0.996999979019165},{"id":"https://openalex.org/keywords/antitumor-immunity","display_name":"antitumor immunity","score":0.753000020980835},{"id":"https://openalex.org/keywords/tumor-microenvironment","display_name":"tumor microenvironment","score":0.6119999885559082},{"id":"https://openalex.org/keywords/breast-cancer","display_name":"breast cancer","score":0.4449999928474426},{"id":"https://openalex.org/keywords/lymphoma","display_name":"lymphoma","score":0.49900001287460327},{"id":"https://openalex.org/keywords/t-cell-persistence","display_name":"T cell persistence","score":0.703000009059906},{"id":"https://openalex.org/keywords/metabolic-reprogramming","display_name":"metabolic reprogramming","score":0.46399998664855957}],"concepts":[{"id":"https://openalex.org/C2776107976","wikidata":"https://www.wikidata.org/wiki/Q1786433","display_name":"Tumor microenvironment","level":3,"score":0.6245062351226807},{"id":"https://openalex.org/C8891405","wikidata":"https://www.wikidata.org/wiki/Q1059","display_name":"Immune system","level":2,"score":0.48461827635765076},{"id":"https://openalex.org/C502942594","wikidata":"https://www.wikidata.org/wiki/Q3421914","display_name":"Cancer research","level":1,"score":0.4776771664619446},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.46344995498657227},{"id":"https://openalex.org/C95444343","wikidata":"https://www.wikidata.org/wiki/Q7141","display_name":"Cell biology","level":1,"score":0.3754615783691406},{"id":"https://openalex.org/C203014093","wikidata":"https://www.wikidata.org/wiki/Q101929","display_name":"Immunology","level":1,"score":0.35020649433135986}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.1182/blood-2022-169006","doi":"https://doi.org/10.1182/blood-2022-169006","is_oa":false,"landing_page_url":"https://doi.org/10.1182/blood-2022-169006","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":[{"id":"https://metadata.un.org/sdg/3","display_name":"Good health and well-being","score":0.98580002784729}],"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/W3111364546","https://openalex.org/W4308453973","https://openalex.org/W3190812922","https://openalex.org/W4324145612","https://openalex.org/W4379386405","https://openalex.org/W3135046911","https://openalex.org/W7162452694","https://openalex.org/W355536126","https://openalex.org/W3157214360","https://openalex.org/W7118017812"],"abstract_inverted_index":{"Chimeric":[0],"antigen":[1],"receptor":[2],"(CAR)":[3],"T":[4,32,63,86,101,106,119,164,172,181,288,294,307,351,383,426,550],"cells":[5,53,107,165,222,289,310,406,532,551],"have":[6],"revolutionized":[7],"the":[8,28,45,55,60,115,168,194,209,216,244,269,339,369,473,505,516,536,546],"treatment":[9,205,285],"of":[10,30,51,131,170,197,206,220,230,286,338,368,374,387,450,462,469,483,491,507,548],"patients":[11],"with":[12,208,290,312,408],"relapsed":[13],"and/or":[14],"refractory":[15],"lymphomas":[16],"resulting":[17],"in":[18,23,34,54,123,227,248,268,302,316,326,349,391,396,404,424,440,477,535,560],"high":[19],"response":[20,249,272],"rates":[21],"even":[22],"heavily":[24],"pretreated":[25],"individuals.":[26],"Despite":[27],"efficacy":[29,196],"CAR":[31,62,171,180,226,549],"therapy":[33],"these":[35,52],"cases,":[36],"long-term":[37,195],"disease":[38],"control":[39,159,330],"remains":[40],"a":[41,89,190,228,293,322,497],"challenge":[42],"owing":[43],"to":[44,85,111,114,126,137,148,153,184,192,250,254,329,360,412,437,454,488,514,544,552],"poor":[46],"persistence":[47,155,217,562],"and":[48,66,78,97,144,156,174,218,282,319,343,354,447,481,509,557,563],"decreased":[49,95],"survival":[50,67],"tumor":[56,158,275,531],"microenvironment":[57],"(TME).":[58],"Within":[59],"TME,":[61,537],"cell":[64,87,150,182,295,352,384,419,427],"activity":[65],"are":[68,109,176,236,265,346,358],"impeded":[69],"by":[70,92,160,252,273,335],"increased":[71,98,215,336],"metabolic":[72,127,438,502,523],"stress":[73,151],"from":[74],"chronic":[75],"stimulation,":[76],"hypoxia,":[77],"limited":[79],"nutrient":[80],"availability.":[81],"This":[82,139,332,394],"ultimately":[83],"leads":[84],"exhaustion,":[88],"state":[90],"characterized":[91],"dysfunctional":[93],"mitochondria,":[94],"proliferation,":[96],"apoptosis.":[99],"Memory":[100],"cells,":[102,120],"particularly":[103],"memory":[104,385,555],"stem":[105],"(Tscm),":[108],"able":[110],"better":[112],"adapt":[113],"TME":[116],"than":[117],"effector":[118,163],"which":[121,345,415,485],"is":[122,333,486,512,527],"part":[124,397],"secondary":[125],"reliance":[128],"on":[129],"\u03b2-oxidation":[130],"fatty":[132,478,493],"acids":[133],"(FAO)":[134],"as":[135,410,496],"opposed":[136],"glycolysis.":[138],"sustains":[140],"mitochondrial":[141],"ATP":[142],"production":[143,187,506],"supports":[145],"antioxidant":[146],"pathways":[147],"limit":[149],"leading":[152,436],"enhanced":[154,492],"improved":[157],"Tscm.":[161],"As":[162,525],"make":[166],"up":[167],"bulk":[169],"products":[173],"Tscm":[175,186,300,327,508],"quite":[177],"rare,":[178],"tuning":[179],"metabolism":[183,457],"enhance":[185,558],"could":[188,540],"be":[189,541],"means":[191],"improve":[193],"cellular":[198,451],"therapies.":[199],"Our":[200],"lab":[201],"previously":[202],"observed":[203,416],"that":[204,241,263,284,298,380,530],"mice":[207],"mammalian":[210],"cyclic":[211],"dinucleotide":[212],"(CDN)":[213],"2'3'-cGAMP":[214,534],"proliferation":[219],"Th/Tc17":[221,309,392,405,441],"expressing":[223],"an":[224],"anti-neu":[225],"model":[229],"locally":[231],"advanced":[232],"breast":[233],"cancer.":[234],"CDNs":[235,357,381,430],"evolutionarily":[237],"conserved":[238],"second":[239],"messengers":[240],"classically":[242],"activate":[243,431],"innate":[245],"immune":[246,271],"system":[247],"pathogens":[251],"binding":[253],"pattern":[255],"recognition":[256],"receptors,":[257],"but":[258],"more":[259],"recent":[260],"data":[261,378,446],"shows":[262],"they":[264],"also":[266,466],"important":[267],"antitumor":[270],"modulating":[274],"immunogenicity.":[276],"We":[277],"now":[278],"extend":[279],"those":[280],"findings":[281],"show":[283,321],"isolated":[287],"cGAMP":[291,313,409,459,521],"induces":[292],"intrinsic":[296],"mechanism":[297],"drives":[299],"formation":[301],"ex":[303],"vivo":[304,561],"expanded":[305],"murine":[306],"cells.":[308,331,393,442],"treated":[311,407],"during":[314],"their":[315,362,554,559],"vitro":[317],"differentiation":[318],"expansion":[320],"5-10":[323],"fold":[324],"increase":[325],"compared":[328,411],"supported":[334],"expression":[337],"transcription":[340],"factors":[341],"Tcf7":[342],"Lef1,":[344],"key":[347,487],"mediators":[348],"maintaining":[350],"stemness":[353],"memory.":[355],"Though":[356],"thought":[359],"mediate":[361],"downstream":[363],"effects":[364],"mainly":[365],"through":[366],"activation":[367,390,464],"adaptor":[370],"protein":[371,434],"STING":[372,389,417],"(stimulator":[373],"interferon":[375],"genes),":[376],"our":[377],"indicates":[379],"promote":[382],"independent":[386],"canonical":[388],"may":[395],"explain":[398],"why":[399],"we":[400,465],"see":[401],"minimal":[402],"cytotoxicity":[403],"prior":[413],"reports":[414],"dependent":[418],"death":[420],"following":[421,458],"CDN":[422],"exposure":[423],"other":[425],"subsets.":[428],"Instead,":[429],"AMPK":[432,463],"(AMP-activated":[433],"kinase)":[435],"reprogramming":[439],"Total":[443],"RNA":[444],"sequencing":[445],"functional":[448],"studies":[449],"bioenergetics":[452,547],"point":[453],"reduced":[455],"glycolytic":[456],"treatment.":[460],"Downstream":[461],"observe":[467],"inhibition":[468],"acetyl-CoA":[470],"carboxylase":[471],"(ACC),":[472],"rate":[474],"limiting":[475],"enzyme":[476],"acid":[479,494],"synthesis,":[480],"upregulation":[482],"Cpt1a":[484],"FAO,":[489],"suggestive":[490],"usage":[495],"fuel":[498],"source.":[499],"Collectively":[500],"this":[501,520,538],"profile":[503],"favors":[504],"further":[510],"work":[511],"ongoing":[513],"delineate":[515],"molecular":[517],"mechanisms":[518],"behind":[519],"triggered":[522],"switch.":[524],"there":[526],"increasing":[528],"evidence":[529],"secrete":[533],"pathway":[539],"readily":[542],"targeted":[543],"manipulate":[545],"maximize":[553],"potential":[556],"function.":[564]},"counts_by_year":[],"updated_date":"2026-10-27T15:51:10.671819","created_date":"2022-11-30T00:00:00"}
