{"id":"https://openalex.org/W7221503733","doi":"https://doi.org/10.3389/fimmu.2026.1934256","title":"Tebentafusp induces systemic immune activation, but tumor immune remodeling remains incompletely validated: a narrative review in metastatic uveal melanoma","display_name":"Tebentafusp induces systemic immune activation, but tumor immune remodeling remains incompletely validated: a narrative review in metastatic uveal melanoma","publication_year":2026,"publication_date":"2026-10-12","ids":{"openalex":"https://openalex.org/W7221503733","doi":"https://doi.org/10.3389/fimmu.2026.1934256","pmid":"https://pubmed.ncbi.nlm.nih.gov/42935816","pmcid":"https://www.ncbi.nlm.nih.gov/pmc/articles/13697601"},"language":"en","primary_location":{"id":"doi:10.3389/fimmu.2026.1934256","doi":"https://doi.org/10.3389/fimmu.2026.1934256","is_oa":true,"landing_page_url":"https://doi.org/10.3389/fimmu.2026.1934256","pdf_url":"https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2026.1934256/pdf","source":{"id":"https://openalex.org/S2595292759","display_name":"Frontiers in Immunology","issn_l":"1664-3224","issn":["1664-3224"],"is_oa":true,"is_in_doaj":true,"is_core":true,"listed_in":["cwts-core","doaj","jufo-1","ki-jl-1","medline","norway-1","poland-140","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320527","host_organization_name":"Frontiers Media","host_organization_lineage":["https://openalex.org/P4310320527"],"host_organization_lineage_names":["Frontiers Media"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Frontiers in Immunology","raw_type":"journal-article"},"volume":null,"type":"review","is_traditional":true,"indexed_in":["crossref","doaj","pubmed"],"open_access":{"is_oa":true,"oa_status":"gold","oa_url":"https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2026.1934256/pdf","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5116446913","display_name":"Francesca Rifaldi","orcid":"https://orcid.org/0009-0003-8475-719X","observed_orcids":["https://orcid.org/0009-0003-8475-719X"]},"institutions":[{"id":"https://openalex.org/I25217355","display_name":"University of Pavia","ror":"https://ror.org/00s6t1f81","country_code":"IT","type":"education","lineage":["https://openalex.org/I25217355"]},{"id":"https://openalex.org/I4210151645","display_name":"Policlinico San Matteo Fondazione","ror":"https://ror.org/05w1q1c88","country_code":"IT","type":"healthcare","lineage":["https://openalex.org/I4210151645","https://openalex.org/I4210153126"]}],"countries":["IT"],"is_corresponding":false,"raw_author_name":"Francesca Rifaldi","raw_affiliation_strings":["Department of Internal Medicine and Medical Therapy, University of Pavia","Department of Oncology, Comprehensive Cancer Center, IRCCS Policlinico San Matteo Foundation"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Internal Medicine and Medical Therapy, University of Pavia","institution_ids":["https://openalex.org/I25217355"]},{"raw_affiliation_string":"Department of Oncology, Comprehensive Cancer Center, IRCCS Policlinico San Matteo Foundation","institution_ids":["https://openalex.org/I4210151645"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5009935310","display_name":"Filippo de Braud","orcid":"https://orcid.org/0000-0003-0103-730X","observed_orcids":["https://orcid.org/0000-0003-0103-730X"]},"institutions":[{"id":"https://openalex.org/I4210156707","display_name":"Fondazione IRCCS Istituto Nazionale dei Tumori","ror":"https://ror.org/05dwj7825","country_code":"IT","type":"healthcare","lineage":["https://openalex.org/I4210153126","https://openalex.org/I4210156707"]}],"countries":["IT"],"is_corresponding":false,"raw_author_name":"Filippo De Braud","raw_affiliation_strings":["Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori","institution_ids":["https://openalex.org/I4210156707"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5000391768","display_name":"Michele Del Vecchio","orcid":"https://orcid.org/0000-0001-9060-2512","observed_orcids":["https://orcid.org/0000-0001-9060-2512"]},"institutions":[{"id":"https://openalex.org/I4210156707","display_name":"Fondazione IRCCS Istituto Nazionale dei Tumori","ror":"https://ror.org/05dwj7825","country_code":"IT","type":"healthcare","lineage":["https://openalex.org/I4210153126","https://openalex.org/I4210156707"]}],"countries":["IT"],"is_corresponding":false,"raw_author_name":"Michele Del Vecchio","raw_affiliation_strings":["Melanoma Medical Oncology Unit, Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Melanoma Medical Oncology Unit, Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori","institution_ids":["https://openalex.org/I4210156707"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5032506137","display_name":"Lorenza Di Guardo","orcid":"https://orcid.org/0000-0002-7297-319X","observed_orcids":["https://orcid.org/0000-0002-7297-319X"]},"institutions":[{"id":"https://openalex.org/I4210156707","display_name":"Fondazione IRCCS Istituto Nazionale dei Tumori","ror":"https://ror.org/05dwj7825","country_code":"IT","type":"healthcare","lineage":["https://openalex.org/I4210153126","https://openalex.org/I4210156707"]}],"countries":["IT"],"is_corresponding":true,"raw_author_name":"Lorenza Di Guardo","raw_affiliation_strings":["Melanoma Medical Oncology Unit, Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Melanoma Medical Oncology Unit, Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori","institution_ids":["https://openalex.org/I4210156707"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":3,"corresponding_author_ids":["https://openalex.org/A5032506137"],"corresponding_institution_ids":["https://openalex.org/I4210156707"],"apc_list":{"value":3150,"currency":"CHF","value_usd":3801},"apc_paid":{"value":3150,"currency":"CHF","value_usd":3801},"fwci":0.0,"has_fulltext":true,"cited_by_count":0,"citation_normalized_percentile":{"value":0.59865219,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":null,"biblio":{"volume":"17","issue":null,"first_page":"1934256","last_page":"1934256"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T11328","display_name":"Ocular Oncology and Treatments","score":0.913100004196167,"subfield":{"id":"https://openalex.org/subfields/2731","display_name":"Ophthalmology"},"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/T11328","display_name":"Ocular Oncology and Treatments","score":0.913100004196167,"subfield":{"id":"https://openalex.org/subfields/2731","display_name":"Ophthalmology"},"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":0.061000000685453415,"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/T11194","display_name":"Ocular Diseases and Beh\u00e7et\u2019s Syndrome","score":0.01769999973475933,"subfield":{"id":"https://openalex.org/subfields/2731","display_name":"Ophthalmology"},"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/tebentafusp","display_name":"tebentafusp","score":1.0},{"id":"https://openalex.org/keywords/metastatic-uveal-melanoma","display_name":"metastatic uveal melanoma","score":0.9769999980926514},{"id":"https://openalex.org/keywords/systemic-immune-activation","display_name":"systemic immune activation","score":0.7839999794960022},{"id":"https://openalex.org/keywords/cytokine-induction","display_name":"cytokine induction","score":0.7609999775886536},{"id":"https://openalex.org/keywords/lymphocyte-changes","display_name":"lymphocyte changes","score":0.7570000290870667},{"id":"https://openalex.org/keywords/cd8-t-cells","display_name":"CD8+ T cells","score":0.6299999952316284},{"id":"https://openalex.org/keywords/interferon-response","display_name":"interferon response","score":0.9620000123977661},{"id":"https://openalex.org/keywords/hla-a-0201","display_name":"HLA-A*0201","score":0.8870000243186951},{"id":"https://openalex.org/keywords/skin-biopsy","display_name":"skin biopsy","score":0.8510000109672546}],"concepts":[{"id":"https://openalex.org/C8891405","wikidata":"https://www.wikidata.org/wiki/Q1059","display_name":"Immune system","level":2,"score":0.7698000073432922},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.7685999870300293},{"id":"https://openalex.org/C2777701055","wikidata":"https://www.wikidata.org/wiki/Q1427096","display_name":"Immunotherapy","level":3,"score":0.4562999904155731},{"id":"https://openalex.org/C167672396","wikidata":"https://www.wikidata.org/wiki/Q417800","display_name":"CD8","level":3,"score":0.4269999861717224},{"id":"https://openalex.org/C2777658100","wikidata":"https://www.wikidata.org/wiki/Q180614","display_name":"Melanoma","level":2,"score":0.4163999855518341},{"id":"https://openalex.org/C143998085","wikidata":"https://www.wikidata.org/wiki/Q162555","display_name":"Oncology","level":1,"score":0.3882000148296356},{"id":"https://openalex.org/C2780851360","wikidata":"https://www.wikidata.org/wiki/Q21686041","display_name":"Immune checkpoint","level":4,"score":0.3700999915599823},{"id":"https://openalex.org/C203014093","wikidata":"https://www.wikidata.org/wiki/Q101929","display_name":"Immunology","level":1,"score":0.3553999960422516},{"id":"https://openalex.org/C2779256057","wikidata":"https://www.wikidata.org/wiki/Q16909647","display_name":"Tumor progression","level":3,"score":0.34369999170303345},{"id":"https://openalex.org/C2777761686","wikidata":"https://www.wikidata.org/wiki/Q715347","display_name":"Lymphocyte","level":2,"score":0.33320000767707825},{"id":"https://openalex.org/C2776914184","wikidata":"https://www.wikidata.org/wiki/Q101991","display_name":"Inflammation","level":2,"score":0.33180001378059387},{"id":"https://openalex.org/C2778690821","wikidata":"https://www.wikidata.org/wiki/Q212354","display_name":"Cytokine","level":2,"score":0.3310999870300293},{"id":"https://openalex.org/C2776252253","wikidata":"https://www.wikidata.org/wiki/Q7663815","display_name":"Systemic inflammation","level":3,"score":0.32919999957084656},{"id":"https://openalex.org/C126322002","wikidata":"https://www.wikidata.org/wiki/Q11180","display_name":"Internal medicine","level":1,"score":0.2937000095844269},{"id":"https://openalex.org/C3020000205","wikidata":"https://www.wikidata.org/wiki/Q2412849","display_name":"Narrative review","level":2,"score":0.28110000491142273},{"id":"https://openalex.org/C188816634","wikidata":"https://www.wikidata.org/wiki/Q2113324","display_name":"Prospective cohort study","level":2,"score":0.271699994802475},{"id":"https://openalex.org/C2776090121","wikidata":"https://www.wikidata.org/wiki/Q193529","display_name":"T cell","level":3,"score":0.27070000767707825},{"id":"https://openalex.org/C72563966","wikidata":"https://www.wikidata.org/wiki/Q1303415","display_name":"Cohort","level":2,"score":0.26649999618530273},{"id":"https://openalex.org/C2779727006","wikidata":"https://www.wikidata.org/wiki/Q426188","display_name":"FOXP3","level":3,"score":0.2590000033378601},{"id":"https://openalex.org/C141341695","wikidata":"https://www.wikidata.org/wiki/Q2368661","display_name":"Surrogate endpoint","level":2,"score":0.2587999999523163},{"id":"https://openalex.org/C2781433595","wikidata":"https://www.wikidata.org/wiki/Q2459042","display_name":"Ipilimumab","level":4,"score":0.2506999969482422}],"mesh":[{"descriptor_ui":"D000098943","descriptor_name":"Uveal Melanoma","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D006801","descriptor_name":"Humans","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D008545","descriptor_name":"Melanoma","qualifier_ui":"Q000188","qualifier_name":"drug therapy","is_major_topic":true},{"descriptor_ui":"D008545","descriptor_name":"Melanoma","qualifier_ui":"Q000276","qualifier_name":"immunology","is_major_topic":true},{"descriptor_ui":"D008545","descriptor_name":"Melanoma","qualifier_ui":"Q000473","qualifier_name":"pathology","is_major_topic":true},{"descriptor_ui":"D009362","descriptor_name":"Neoplasm Metastasis","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D014604","descriptor_name":"Uveal Neoplasms","qualifier_ui":"Q000188","qualifier_name":"drug therapy","is_major_topic":true},{"descriptor_ui":"D014604","descriptor_name":"Uveal Neoplasms","qualifier_ui":"Q000276","qualifier_name":"immunology","is_major_topic":true},{"descriptor_ui":"D014604","descriptor_name":"Uveal Neoplasms","qualifier_ui":"Q000473","qualifier_name":"pathology","is_major_topic":true},{"descriptor_ui":"D016207","descriptor_name":"Cytokines","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D059016","descriptor_name":"Tumor Microenvironment","qualifier_ui":"Q000187","qualifier_name":"drug effects","is_major_topic":false},{"descriptor_ui":"D059016","descriptor_name":"Tumor Microenvironment","qualifier_ui":"Q000276","qualifier_name":"immunology","is_major_topic":false}],"locations_count":4,"locations":[{"id":"doi:10.3389/fimmu.2026.1934256","doi":"https://doi.org/10.3389/fimmu.2026.1934256","is_oa":true,"landing_page_url":"https://doi.org/10.3389/fimmu.2026.1934256","pdf_url":"https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2026.1934256/pdf","source":{"id":"https://openalex.org/S2595292759","display_name":"Frontiers in Immunology","issn_l":"1664-3224","issn":["1664-3224"],"is_oa":true,"is_in_doaj":true,"is_core":true,"listed_in":["cwts-core","doaj","jufo-1","ki-jl-1","medline","norway-1","poland-140","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320527","host_organization_name":"Frontiers Media","host_organization_lineage":["https://openalex.org/P4310320527"],"host_organization_lineage_names":["Frontiers Media"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Frontiers in Immunology","raw_type":"journal-article"},{"id":"pmh:oai:pubmedcentral.nih.gov:13697601","doi":null,"is_oa":true,"landing_page_url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC13697601/","pdf_url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC13697601/pdf/fimmu-17-1934256.pdf","source":{"id":"https://openalex.org/S2764455111","display_name":"PubMed Central","issn_l":null,"issn":null,"is_oa":true,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Front Immunol","raw_type":"Text"},{"id":"pmid:42935816","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/42935816","pdf_url":null,"source":{"id":"https://openalex.org/S4306525036","display_name":"PubMed","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Frontiers in immunology","raw_type":"Journal Article"},{"id":"pmh:oai:doaj.org/article:3efeed60adc94a57a40274ab7ae7c649","doi":null,"is_oa":false,"landing_page_url":"https://doaj.org/article/3efeed60adc94a57a40274ab7ae7c649","pdf_url":null,"source":{"id":"https://openalex.org/S4306401280","display_name":"DOAJ (DOAJ: Directory of Open Access Journals)","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":"repository"},"license":null,"license_id":null,"version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"Frontiers in Immunology, Vol 17 (2026)","raw_type":"article"}],"best_oa_location":{"id":"doi:10.3389/fimmu.2026.1934256","doi":"https://doi.org/10.3389/fimmu.2026.1934256","is_oa":true,"landing_page_url":"https://doi.org/10.3389/fimmu.2026.1934256","pdf_url":"https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2026.1934256/pdf","source":{"id":"https://openalex.org/S2595292759","display_name":"Frontiers in Immunology","issn_l":"1664-3224","issn":["1664-3224"],"is_oa":true,"is_in_doaj":true,"is_core":true,"listed_in":["cwts-core","doaj","jufo-1","ki-jl-1","medline","norway-1","poland-140","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320527","host_organization_name":"Frontiers Media","host_organization_lineage":["https://openalex.org/P4310320527"],"host_organization_lineage_names":["Frontiers Media"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Frontiers in Immunology","raw_type":"journal-article"},"sustainable_development_goals":[{"display_name":"Good health and well-being","score":1.0,"id":"https://metadata.un.org/sdg/3"}],"study_designs":[],"awards":[],"funders":[],"has_content":{"pdf":true,"grobid_xml":true},"content_urls":{"pdf":"https://content.openalex.org/works/W7221503733.pdf","grobid_xml":"https://content.openalex.org/works/W7221503733.grobid-xml"},"referenced_works_count":15,"referenced_works":["https://openalex.org/W2990648940","https://openalex.org/W3118615836","https://openalex.org/W3182312709","https://openalex.org/W3200574709","https://openalex.org/W4211226125","https://openalex.org/W4220675084","https://openalex.org/W4282980190","https://openalex.org/W4308399147","https://openalex.org/W4388042783","https://openalex.org/W4393088752","https://openalex.org/W4403378262","https://openalex.org/W4408282309","https://openalex.org/W4409446817","https://openalex.org/W4410003866","https://openalex.org/W4415900201"],"related_works":["https://openalex.org/W3182312709","https://openalex.org/W7167057114","https://openalex.org/W7106307957","https://openalex.org/W4205670716","https://openalex.org/W3200574709","https://openalex.org/W7221564288","https://openalex.org/W4412430841","https://openalex.org/W7217044162","https://openalex.org/W4415216038","https://openalex.org/W4399128232"],"abstract_inverted_index":{"Background:":[0],"Tebentafusp":[1,197],"improves":[2],"survival":[3,175],"in":[4,50,176],"HLA-A*02:01-positive":[5],"metastatic":[6,21,193,212],"uveal":[7,52],"melanoma,":[8],"yet":[9],"the":[10],"human":[11,42],"evidence":[12,39,112,183,191,221],"linking":[13,251],"early":[14,131,203],"systemic":[15,204],"immune":[16,48,170,205,214,246,252],"activation":[17,206],"to":[18,66,81,254],"remodeling":[19,215],"of":[20,41,165,184],"tumors":[22],"is":[23,198],"dispersed":[24],"across":[25,207],"overlapping":[26,163,208],"translational":[27],"reports.":[28],"Methods:":[29],"We":[30],"performed":[31],"a":[32,227],"PRISMA-style,":[33],"search-informed":[34],"narrative":[35],"review":[36],"and":[37,56,103,121,134,147,151,168,239,248],"descriptive":[38],"mapping":[40],"reports":[43,61,97,105],"evaluating":[44],"baseline":[45],"or":[46,85,98],"on-treatment":[47,169],"measurements":[49],"tebentafusp-treated":[51],"melanoma.":[53],"PubMed/MEDLINE,":[54],"Embase,":[55],"CENTRAL":[57],"were":[58,79,93,101,106,172],"searched":[59],"for":[60],"published":[62],"from":[63,162],"January":[64],"2015":[65],"9":[67,75],"December":[68],"2025,":[69],"with":[70,174,200],"an":[71,122],"updated":[72],"search":[73],"on":[74],"June":[76],"2026.":[77],"Reports":[78],"linked":[80],"their":[82],"underlying":[83],"trial":[84],"cohort":[86],"before":[87],"synthesis.":[88],"Results:":[89],"Overall,":[90],"286":[91],"records":[92],"screened,":[94],"21":[95],"full-text":[96],"complete":[99],"abstracts":[100],"assessed,":[102],"10":[104,116],"retained.":[107],"These":[108],"represented":[109],"three":[110],"principal":[111],"units":[113],"rather":[114,225],"than":[115,226],"independent":[117,123,182],"studies:":[118],"NCT02570308,":[119],"NCT03070392,":[120],"serial":[124],"skin-biopsy":[125],"cohort.":[126],"Blood-based":[127],"analyses":[128,143,164,250],"consistently":[129,201],"showed":[130],"cytokine":[132],"induction":[133],"transient":[135],"lymphocyte":[136],"changes":[137,253],"after":[138],"tebentafusp":[139],"dosing.":[140],"Paired":[141],"metastatic-tissue":[142],"reported":[144],"increased":[145],"CD3":[146],"CD8":[148],"cell":[149],"density":[150],"interferon-response":[152],"programs":[153],"by":[154],"day":[155],"16,":[156],"but":[157,188,210],"these":[158],"observations":[159],"derived":[160],"predominantly":[161],"NCT02570308.":[166],"Baseline":[167],"features":[171],"associated":[173,199],"exploratory":[177],"analyses.":[178],"Skin":[179],"biopsies":[180],"provided":[181],"on-target":[185],"cutaneous":[186],"pharmacodynamics":[187],"only":[189],"indirect":[190],"regarding":[192],"tumor":[194,213],"remodeling.":[195],"Conclusion:":[196],"observed":[202],"analyses,":[209],"treatment-associated":[211],"remains":[216],"incompletely":[217],"validated.":[218],"The":[219],"available":[220],"supports":[222],"temporal":[223],"coherence":[224],"proven":[228],"causal":[229],"systemic-to-tumor":[230],"pathway.":[231],"Future":[232],"studies":[233],"should":[234],"use":[235],"prospective":[236],"paired":[237],"blood":[238],"liver":[240],"sampling,":[241],"harmonized":[242],"time":[243],"points,":[244],"prespecified":[245],"endpoints,":[247],"mediation":[249],"clinical":[255],"outcomes.":[256]},"counts_by_year":[],"updated_date":"2026-10-31T12:09:11.096373","created_date":"2026-10-13T00:00:00"}