{"id":"https://openalex.org/W7225458043","doi":"https://doi.org/10.1007/s00262-026-04612-8","title":"Tumor heterogeneity shapes responses to STING and LT\u03b2R-mediated TLS induction","display_name":"Tumor heterogeneity shapes responses to STING and LT\u03b2R-mediated TLS induction","publication_year":2026,"publication_date":"2026-11-07","ids":{"openalex":"https://openalex.org/W7225458043","doi":"https://doi.org/10.1007/s00262-026-04612-8"},"language":"en","primary_location":{"id":"doi:10.1007/s00262-026-04612-8","doi":"https://doi.org/10.1007/s00262-026-04612-8","is_oa":true,"landing_page_url":"https://doi.org/10.1007/s00262-026-04612-8","pdf_url":null,"source":{"id":"https://openalex.org/S203303425","display_name":"Cancer Immunology Immunotherapy","issn_l":"0340-7004","issn":["0340-7004","1432-0851"],"is_oa":true,"is_in_doaj":true,"is_core":true,"listed_in":["cwts-core","doaj","dongbi-b","doyens","jufo-1","ki-jl-1","medline","norway-1","poland-140","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310319900","host_organization_name":"Springer Science+Business Media","host_organization_lineage":["https://openalex.org/P4310319900","https://openalex.org/P4310319965"],"host_organization_lineage_names":["Springer Science+Business Media","Springer Nature"],"type":"journal"},"license":"cc-by-nc-nd","license_id":"https://openalex.org/licenses/cc-by-nc-nd","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Cancer Immunology, Immunotherapy","raw_type":"journal-article"},"volume":null,"type":"article","is_traditional":true,"indexed_in":["crossref","doaj"],"open_access":{"is_oa":true,"oa_status":"gold","oa_url":"https://doi.org/10.1007/s00262-026-04612-8","any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5064743740","display_name":"Fernanda Arag\u00e3o Felix","orcid":"https://orcid.org/0000-0003-3054-4642","observed_orcids":["https://orcid.org/0000-0003-3054-4642"]},"institutions":[{"id":"https://openalex.org/I145311948","display_name":"Johns Hopkins University","ror":"https://ror.org/00za53h95","country_code":"US","type":"education","lineage":["https://openalex.org/I145311948"]},{"id":"https://openalex.org/I4210098865","display_name":"Johns Hopkins All Children's Hospital","ror":"https://ror.org/013x5cp73","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I2799853436","https://openalex.org/I4210098865"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Fernanda Arag\u00e3o Felix","raw_affiliation_strings":["Cancer and Blood Disorders Institute (CBDI), Johns Hopkins All Children\u2019s Hospital, St. Petersburg, Florida, USA","Department of Orthopaedic Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA","Institute for Fundamental Biomedical Research (IFBR), Johns Hopkins All Children\u2019s Hospital, St. Petersburg, Florida, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Cancer and Blood Disorders Institute (CBDI), Johns Hopkins All Children\u2019s Hospital, St. Petersburg, Florida, USA","institution_ids":["https://openalex.org/I4210098865"]},{"raw_affiliation_string":"Department of Orthopaedic Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA","institution_ids":["https://openalex.org/I145311948"]},{"raw_affiliation_string":"Institute for Fundamental Biomedical Research (IFBR), Johns Hopkins All Children\u2019s Hospital, St. Petersburg, Florida, USA","institution_ids":["https://openalex.org/I4210098865"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5161219200","display_name":"Azizur Rahman","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I145311948","display_name":"Johns Hopkins University","ror":"https://ror.org/00za53h95","country_code":"US","type":"education","lineage":["https://openalex.org/I145311948"]},{"id":"https://openalex.org/I4210098865","display_name":"Johns Hopkins All Children's Hospital","ror":"https://ror.org/013x5cp73","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I2799853436","https://openalex.org/I4210098865"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Azizur Rahman","raw_affiliation_strings":["Cancer and Blood Disorders Institute (CBDI), Johns Hopkins All Children\u2019s Hospital, St. Petersburg, Florida, USA","Department of Orthopaedic Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA","Institute for Fundamental Biomedical Research (IFBR), Johns Hopkins All Children\u2019s Hospital, St. Petersburg, Florida, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Cancer and Blood Disorders Institute (CBDI), Johns Hopkins All Children\u2019s Hospital, St. Petersburg, Florida, USA","institution_ids":["https://openalex.org/I4210098865"]},{"raw_affiliation_string":"Department of Orthopaedic Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA","institution_ids":["https://openalex.org/I145311948"]},{"raw_affiliation_string":"Institute for Fundamental Biomedical Research (IFBR), Johns Hopkins All Children\u2019s Hospital, St. Petersburg, Florida, USA","institution_ids":["https://openalex.org/I4210098865"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5161200755","display_name":"Ashley A. Becker","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I145311948","display_name":"Johns Hopkins University","ror":"https://ror.org/00za53h95","country_code":"US","type":"education","lineage":["https://openalex.org/I145311948"]},{"id":"https://openalex.org/I4210098865","display_name":"Johns Hopkins All Children's Hospital","ror":"https://ror.org/013x5cp73","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I2799853436","https://openalex.org/I4210098865"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Ashley A. Becker","raw_affiliation_strings":["Cancer and Blood Disorders Institute (CBDI), Johns Hopkins All Children\u2019s Hospital, St. Petersburg, Florida, USA","Department of Orthopaedic Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA","Institute for Fundamental Biomedical Research (IFBR), Johns Hopkins All Children\u2019s Hospital, St. Petersburg, Florida, USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Cancer and Blood Disorders Institute (CBDI), Johns Hopkins All Children\u2019s Hospital, St. Petersburg, Florida, USA","institution_ids":["https://openalex.org/I4210098865"]},{"raw_affiliation_string":"Department of Orthopaedic Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA","institution_ids":["https://openalex.org/I145311948"]},{"raw_affiliation_string":"Institute for Fundamental Biomedical Research (IFBR), Johns Hopkins All Children\u2019s Hospital, St. Petersburg, Florida, USA","institution_ids":["https://openalex.org/I4210098865"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5079503178","display_name":"Junko Sawada","orcid":"https://orcid.org/0000-0001-9100-7037","observed_orcids":["https://orcid.org/0000-0001-9100-7037"]},"institutions":[{"id":"https://openalex.org/I145311948","display_name":"Johns Hopkins University","ror":"https://ror.org/00za53h95","country_code":"US","type":"education","lineage":["https://openalex.org/I145311948"]},{"id":"https://openalex.org/I4210098865","display_name":"Johns Hopkins All Children's Hospital","ror":"https://ror.org/013x5cp73","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I2799853436","https://openalex.org/I4210098865"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"Junko Sawada","raw_affiliation_strings":["Cancer and Blood Disorders Institute (CBDI), Johns Hopkins All Children\u2019s Hospital, St. Petersburg, Florida, USA","Department of Orthopaedic Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA","Institute for Fundamental Biomedical Research (IFBR), Johns Hopkins All Children\u2019s Hospital, St. Petersburg, Florida, USA"],"raw_orcid":"https://orcid.org/0000-0001-9100-7037","affiliations":[{"raw_affiliation_string":"Cancer and Blood Disorders Institute (CBDI), Johns Hopkins All Children\u2019s Hospital, St. Petersburg, Florida, USA","institution_ids":["https://openalex.org/I4210098865"]},{"raw_affiliation_string":"Department of Orthopaedic Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA","institution_ids":["https://openalex.org/I145311948"]},{"raw_affiliation_string":"Institute for Fundamental Biomedical Research (IFBR), Johns Hopkins All Children\u2019s Hospital, St. Petersburg, Florida, USA","institution_ids":["https://openalex.org/I4210098865"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":2,"corresponding_author_ids":["https://openalex.org/A5079503178"],"corresponding_institution_ids":["https://openalex.org/I145311948","https://openalex.org/I4210098865"],"apc_list":{"value":4590,"currency":"USD","value_usd":4590},"apc_paid":{"value":4590,"currency":"USD","value_usd":4590},"fwci":0.0,"has_fulltext":false,"cited_by_count":0,"citation_normalized_percentile":{"value":0.0,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"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/T10158","display_name":"Cancer Immunotherapy and Biomarkers","score":0.9473000168800354,"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":0.9473000168800354,"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/T10231","display_name":"Pancreatic and Hepatic Oncology Research","score":0.017799999564886093,"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":0.012199999764561653,"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/tertiary-lymphoid-structures","display_name":"tertiary lymphoid structures","score":0.9929999709129333},{"id":"https://openalex.org/keywords/tumor-heterogeneity","display_name":"tumor heterogeneity","score":0.8759999871253967},{"id":"https://openalex.org/keywords/sting","display_name":"STING","score":0.8420000076293945},{"id":"https://openalex.org/keywords/lymphotoxin-beta-receptor","display_name":"lymphotoxin beta receptor","score":0.9020000100135803},{"id":"https://openalex.org/keywords/tumor-microenvironment","display_name":"tumor microenvironment","score":0.5550000071525574},{"id":"https://openalex.org/keywords/pancreatic-cancer","display_name":"pancreatic cancer","score":0.9539999961853027},{"id":"https://openalex.org/keywords/kpc-mice","display_name":"KPC mice","score":0.8029999732971191},{"id":"https://openalex.org/keywords/antitumor-immunity","display_name":"antitumor immunity","score":0.9020000100135803},{"id":"https://openalex.org/keywords/stromal-remodeling","display_name":"stromal remodeling","score":0.8370000123977661},{"id":"https://openalex.org/keywords/extracellular-matrix-remodeling","display_name":"extracellular matrix remodeling","score":0.8669999837875366},{"id":"https://openalex.org/keywords/tgf-beta-signaling","display_name":"TGF-beta signaling","score":0.8460000157356262},{"id":"https://openalex.org/keywords/cancer-transcriptomics","display_name":"cancer transcriptomics","score":0.4690000116825104},{"id":"https://openalex.org/keywords/tumor-infiltrating-immune-cells","display_name":"tumor-infiltrating immune cells","score":0.47999998927116394}],"concepts":[{"id":"https://openalex.org/C189165786","wikidata":"https://www.wikidata.org/wiki/Q193825","display_name":"Extracellular matrix","level":2,"score":0.6851000189781189},{"id":"https://openalex.org/C2780210213","wikidata":"https://www.wikidata.org/wiki/Q212961","display_name":"Pancreatic cancer","level":3,"score":0.6384000182151794},{"id":"https://openalex.org/C16930146","wikidata":"https://www.wikidata.org/wiki/Q4381253","display_name":"Stromal cell","level":2,"score":0.6301000118255615},{"id":"https://openalex.org/C502942594","wikidata":"https://www.wikidata.org/wiki/Q3421914","display_name":"Cancer research","level":1,"score":0.6082000136375427},{"id":"https://openalex.org/C162317418","wikidata":"https://www.wikidata.org/wiki/Q252857","display_name":"Transcriptome","level":4,"score":0.5515999794006348},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.5198000073432922},{"id":"https://openalex.org/C2776107976","wikidata":"https://www.wikidata.org/wiki/Q1786433","display_name":"Tumor microenvironment","level":3,"score":0.4952999949455261},{"id":"https://openalex.org/C2779341262","wikidata":"https://www.wikidata.org/wiki/Q182581","display_name":"Immunity","level":3,"score":0.4343000054359436},{"id":"https://openalex.org/C121608353","wikidata":"https://www.wikidata.org/wiki/Q12078","display_name":"Cancer","level":2,"score":0.4043999910354614},{"id":"https://openalex.org/C203014093","wikidata":"https://www.wikidata.org/wiki/Q101929","display_name":"Immunology","level":1,"score":0.4011000096797943},{"id":"https://openalex.org/C24998067","wikidata":"https://www.wikidata.org/wiki/Q4114622","display_name":"Stimulation","level":2,"score":0.38359999656677246},{"id":"https://openalex.org/C2779256057","wikidata":"https://www.wikidata.org/wiki/Q16909647","display_name":"Tumor progression","level":3,"score":0.38190001249313354},{"id":"https://openalex.org/C2777701055","wikidata":"https://www.wikidata.org/wiki/Q1427096","display_name":"Immunotherapy","level":3,"score":0.36469998955726624},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.3537999987602234},{"id":"https://openalex.org/C8891405","wikidata":"https://www.wikidata.org/wiki/Q1059","display_name":"Immune system","level":2,"score":0.30219998955726624},{"id":"https://openalex.org/C165864922","wikidata":"https://www.wikidata.org/wiki/Q411391","display_name":"Regulation of gene expression","level":3,"score":0.29440000653266907},{"id":"https://openalex.org/C127561419","wikidata":"https://www.wikidata.org/wiki/Q224527","display_name":"Downregulation and upregulation","level":3,"score":0.2833000123500824},{"id":"https://openalex.org/C2777996000","wikidata":"https://www.wikidata.org/wiki/Q7130412","display_name":"Pancreatic tumor","level":4,"score":0.2802000045776367},{"id":"https://openalex.org/C2778690821","wikidata":"https://www.wikidata.org/wiki/Q212354","display_name":"Cytokine","level":2,"score":0.2802000045776367},{"id":"https://openalex.org/C2777007597","wikidata":"https://www.wikidata.org/wiki/Q16869243","display_name":"Stromal tumor","level":3,"score":0.2750999927520752},{"id":"https://openalex.org/C28406088","wikidata":"https://www.wikidata.org/wiki/Q5571762","display_name":"Extracellular","level":2,"score":0.27239999175071716},{"id":"https://openalex.org/C150194340","wikidata":"https://www.wikidata.org/wiki/Q26972","display_name":"Gene expression","level":3,"score":0.26840001344680786},{"id":"https://openalex.org/C96232424","wikidata":"https://www.wikidata.org/wiki/Q4118072","display_name":"Cancer cell","level":3,"score":0.2597000002861023},{"id":"https://openalex.org/C3017875465","wikidata":"https://www.wikidata.org/wiki/Q189146","display_name":"Cellular immunity","level":3,"score":0.25609999895095825},{"id":"https://openalex.org/C17991360","wikidata":"https://www.wikidata.org/wiki/Q21173843","display_name":"Tumor necrosis factor alpha","level":2,"score":0.2506999969482422}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.1007/s00262-026-04612-8","doi":"https://doi.org/10.1007/s00262-026-04612-8","is_oa":true,"landing_page_url":"https://doi.org/10.1007/s00262-026-04612-8","pdf_url":null,"source":{"id":"https://openalex.org/S203303425","display_name":"Cancer Immunology Immunotherapy","issn_l":"0340-7004","issn":["0340-7004","1432-0851"],"is_oa":true,"is_in_doaj":true,"is_core":true,"listed_in":["cwts-core","doaj","dongbi-b","doyens","jufo-1","ki-jl-1","medline","norway-1","poland-140","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310319900","host_organization_name":"Springer Science+Business Media","host_organization_lineage":["https://openalex.org/P4310319900","https://openalex.org/P4310319965"],"host_organization_lineage_names":["Springer Science+Business Media","Springer Nature"],"type":"journal"},"license":"cc-by-nc-nd","license_id":"https://openalex.org/licenses/cc-by-nc-nd","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Cancer Immunology, Immunotherapy","raw_type":"journal-article"}],"best_oa_location":{"id":"doi:10.1007/s00262-026-04612-8","doi":"https://doi.org/10.1007/s00262-026-04612-8","is_oa":true,"landing_page_url":"https://doi.org/10.1007/s00262-026-04612-8","pdf_url":null,"source":{"id":"https://openalex.org/S203303425","display_name":"Cancer Immunology Immunotherapy","issn_l":"0340-7004","issn":["0340-7004","1432-0851"],"is_oa":true,"is_in_doaj":true,"is_core":true,"listed_in":["cwts-core","doaj","dongbi-b","doyens","jufo-1","ki-jl-1","medline","norway-1","poland-140","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310319900","host_organization_name":"Springer Science+Business Media","host_organization_lineage":["https://openalex.org/P4310319900","https://openalex.org/P4310319965"],"host_organization_lineage_names":["Springer Science+Business Media","Springer Nature"],"type":"journal"},"license":"cc-by-nc-nd","license_id":"https://openalex.org/licenses/cc-by-nc-nd","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Cancer Immunology, Immunotherapy","raw_type":"journal-article"},"sustainable_development_goals":[{"display_name":"Good health and well-being","score":0.9922999739646912,"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/W7130605706","https://openalex.org/W7148775627","https://openalex.org/W7130310621","https://openalex.org/W4415900258","https://openalex.org/W4407866619","https://openalex.org/W4384559924","https://openalex.org/W3179443060","https://openalex.org/W7155623962","https://openalex.org/W7162667021","https://openalex.org/W2423943388"],"abstract_inverted_index":{"Tertiary":[0],"lymphoid":[1],"structures":[2],"(TLSs)":[3],"are":[4],"associated":[5,161],"with":[6,162],"improved":[7],"anti-tumor":[8,29,73],"immunity":[9,30],"and":[10,63,98,110,123,126,156],"favorable":[11],"clinical":[12],"outcomes":[13],"across":[14,75],"multiple":[15],"cancer":[16,32,50],"types.":[17],"Therapeutic":[18],"induction":[19,43,155],"of":[20,37,60,104,121],"TLSs":[21],"is":[22],"a":[23,163],"promising":[24],"strategy":[25],"to":[26,131,152],"stimulate":[27],"potent":[28],"in":[31,84,116],"patients.":[33],"However,":[34],"the":[35,58,119,136],"impact":[36],"tumor":[38,76,128,147,165],"heterogeneity":[39,148],"on":[40,66],"therapeutic":[41,153],"TLS":[42,67,79,140,154],"remains":[44],"poorly":[45],"understood.":[46],"Using":[47],"four":[48],"pancreatic":[49,146],"models":[51],"derived":[52],"from":[53],"KPC":[54],"mice,":[55],"we":[56],"examined":[57],"effect":[59],"combined":[61],"STING":[62],"LT\u03b2R":[64],"stimulation":[65,132],"induction.":[68],"Although":[69],"treatment":[70],"elicited":[71],"variable":[72],"responses":[74],"models,":[77],"robust":[78],"formation":[80],"was":[81],"observed":[82],"only":[83],"KxPxCx":[85,93],"tumors.":[86],"Comparative":[87],"transcriptomic":[88],"analyses":[89],"demonstrated":[90],"that":[91,145],"TLS-permissive":[92,164],"tumors":[94],"exhibited":[95],"distinct":[96,158],"inflammatory":[97],"stromal":[99],"remodeling":[100],"programs,":[101],"including":[102],"enrichment":[103],"fibroblastic,":[105],"extracellular":[106],"matrix":[107],"remodeling,":[108],"wound-healing,":[109],"TGF\u03b2-associated":[111],"pathways.":[112],"Despite":[113],"these":[114],"differences":[115],"transcriptional":[117,159],"profiles,":[118],"expression":[120],"STING-":[122],"LT\u03b2R-associated":[124],"proteins":[125],"direct":[127],"cell":[129],"responsiveness":[130,151],"did":[133],"not":[134],"explain":[135],"selective":[137],"capacity":[138],"for":[139],"formation.":[141],"These":[142],"findings":[143],"demonstrate":[144],"profoundly":[149],"influences":[150],"identify":[157],"characteristics":[160],"microenvironment.":[166]},"counts_by_year":[],"updated_date":"2026-11-09T13:22:03.289127","created_date":"2026-11-08T00:00:00"}
