{"id":"https://openalex.org/W7125597602","doi":"https://doi.org/10.33696/cancerimmunol.7.113","title":"Next-Generation Immune Checkpoint Inhibitors in Cancer: Mechanisms, Current Clinical Advances, and Future Directions","display_name":"Next-Generation Immune Checkpoint Inhibitors in Cancer: Mechanisms, Current Clinical Advances, and Future Directions","publication_year":2025,"publication_date":"2025-12-20","ids":{"openalex":"https://openalex.org/W7125597602","doi":"https://doi.org/10.33696/cancerimmunol.7.113"},"language":"en","primary_location":{"id":"doi:10.33696/cancerimmunol.7.113","doi":"https://doi.org/10.33696/cancerimmunol.7.113","is_oa":true,"landing_page_url":"https://doi.org/10.33696/cancerimmunol.7.113","pdf_url":"https://www.scientificarchives.com/public/assets/articles/article-pdf-1766229657-1610.pdf","source":{"id":"https://openalex.org/S4387278351","display_name":"Journal of Cancer Immunology","issn_l":"2689-968X","issn":["2689-968X"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core"],"host_organization":"https://openalex.org/P4323867245","host_organization_name":"Scientific Archives LLC","host_organization_lineage":["https://openalex.org/P4323867245"],"host_organization_lineage_names":["Scientific Archives LLC"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Journal of Cancer Immunology","raw_type":"journal-article"},"volume":null,"type":"article","indexed_in":["crossref"],"open_access":{"is_oa":true,"oa_status":"hybrid","oa_url":"https://www.scientificarchives.com/public/assets/articles/article-pdf-1766229657-1610.pdf","any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5119612949","display_name":"Tabish Hussain","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I1343551460","display_name":"The University of Texas MD Anderson Cancer Center","ror":"https://ror.org/04twxam07","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I1343551460"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"Tabish Hussain","raw_affiliation_strings":["Department of Genetics , The University of Texas MD Anderson Cancer Center , Houston , TX , USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Genetics , The University of Texas MD Anderson Cancer Center , Houston , TX , USA","institution_ids":["https://openalex.org/I1343551460"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5047550576","display_name":"Dhurjhoti Saha","orcid":"https://orcid.org/0000-0001-6009-9274","observed_orcids":["https://orcid.org/0000-0001-6009-9274"]},"institutions":[{"id":"https://openalex.org/I1343551460","display_name":"The University of Texas MD Anderson Cancer Center","ror":"https://ror.org/04twxam07","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I1343551460"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Dhurjhoti Saha","raw_affiliation_strings":["Department of Epigenetics and Molecular Carcinogenesis , The University of Texas MD Anderson Cancer Center , Houston , TX , USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Epigenetics and Molecular Carcinogenesis , The University of Texas MD Anderson Cancer Center , Houston , TX , USA","institution_ids":["https://openalex.org/I1343551460"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5028693685","display_name":"Abhijit Chakraborty","orcid":"https://orcid.org/0000-0002-3822-5657","observed_orcids":["https://orcid.org/0000-0002-3822-5657"]},"institutions":[{"id":"https://openalex.org/I1343551460","display_name":"The University of Texas MD Anderson Cancer Center","ror":"https://ror.org/04twxam07","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I1343551460"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"Abhijit Chakraborty","raw_affiliation_strings":["Department of Investigational Cancer Therapeutics , The University of Texas MD Anderson Cancer Center , Houston , TX , USA"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Investigational Cancer Therapeutics , The University of Texas MD Anderson Cancer Center , Houston , TX , USA","institution_ids":["https://openalex.org/I1343551460"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"corresponding_author_ids":["https://openalex.org/A5028693685","https://openalex.org/A5119612949"],"corresponding_institution_ids":["https://openalex.org/I1343551460"],"apc_list":null,"apc_paid":null,"fwci":1.6564,"has_fulltext":true,"cited_by_count":4,"citation_normalized_percentile":{"value":0.8664797,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":{"min":98,"max":99},"biblio":{"volume":"7","issue":"3","first_page":"144","last_page":"144"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10158","display_name":"Cancer Immunotherapy and Biomarkers","score":1.0,"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":1.0,"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":0.0,"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/immune-checkpoint-inhibitors","display_name":"immune checkpoint inhibitors","score":0.9900000095367432},{"id":"https://openalex.org/keywords/ctla-4","display_name":"CTLA-4","score":0.8970000147819519},{"id":"https://openalex.org/keywords/pd-1-pd-l1","display_name":"PD-1/PD-L1","score":0.9729999899864197},{"id":"https://openalex.org/keywords/lag-3","display_name":"LAG-3","score":0.8330000042915344},{"id":"https://openalex.org/keywords/tigit","display_name":"TIGIT","score":0.9959999918937683},{"id":"https://openalex.org/keywords/tim-3","display_name":"TIM-3","score":0.9990000128746033},{"id":"https://openalex.org/keywords/vista","display_name":"VISTA","score":0.996999979019165},{"id":"https://openalex.org/keywords/nkg2a","display_name":"NKG2A","score":0.9769999980926514},{"id":"https://openalex.org/keywords/siglec-15","display_name":"Siglec-15","score":0.9959999918937683},{"id":"https://openalex.org/keywords/ox40","display_name":"OX40","score":0.8600000143051147},{"id":"https://openalex.org/keywords/4-1bb","display_name":"4-1BB","score":0.9950000047683716},{"id":"https://openalex.org/keywords/inducible-t-cell-costimulator","display_name":"ICOS","score":0.9929999709129333},{"id":"https://openalex.org/keywords/gitr","display_name":"GITR","score":0.9980000257492065},{"id":"https://openalex.org/keywords/cd40","display_name":"CD40","score":0.9869999885559082},{"id":"https://openalex.org/keywords/t-cell-exhaustion","display_name":"T cell exhaustion","score":0.7919999957084656},{"id":"https://openalex.org/keywords/tumor-microenvironment","display_name":"tumor microenvironment","score":0.5920000076293945},{"id":"https://openalex.org/keywords/immune-related-adverse-events","display_name":"immune-related adverse events","score":0.7279999852180481},{"id":"https://openalex.org/keywords/immune-checkpoint-inhibitor-resistance","display_name":"immune checkpoint inhibitor resistance","score":0.5550000071525574},{"id":"https://openalex.org/keywords/biomarker-driven-patient-selection","display_name":"biomarker-driven patient selection","score":0.7850000262260437},{"id":"https://openalex.org/keywords/multispecific-antibodies","display_name":"multispecific antibodies","score":0.9380000233650208},{"id":"https://openalex.org/keywords/engineered-cytokines","display_name":"engineered cytokines","score":0.9779999852180481},{"id":"https://openalex.org/keywords/cancer-immunotherapy","display_name":"cancer immunotherapy","score":0.8100000023841858}],"concepts":[{"id":"https://openalex.org/C2777701055","wikidata":"https://www.wikidata.org/wiki/Q1427096","display_name":"Immunotherapy","level":3,"score":0.6632000207901001},{"id":"https://openalex.org/C2780674031","wikidata":"https://www.wikidata.org/wiki/Q2012719","display_name":"Cancer immunotherapy","level":4,"score":0.5307000279426575},{"id":"https://openalex.org/C8891405","wikidata":"https://www.wikidata.org/wiki/Q1059","display_name":"Immune system","level":2,"score":0.5088000297546387},{"id":"https://openalex.org/C502942594","wikidata":"https://www.wikidata.org/wiki/Q3421914","display_name":"Cancer research","level":1,"score":0.48429998755455017},{"id":"https://openalex.org/C154317977","wikidata":"https://www.wikidata.org/wiki/Q376266","display_name":"Cytotoxic T cell","level":3,"score":0.478300005197525},{"id":"https://openalex.org/C2780851360","wikidata":"https://www.wikidata.org/wiki/Q21686041","display_name":"Immune checkpoint","level":4,"score":0.476500004529953},{"id":"https://openalex.org/C2781053074","wikidata":"https://www.wikidata.org/wiki/Q21100639","display_name":"PD-L1","level":4,"score":0.4650999903678894},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.4593999981880188},{"id":"https://openalex.org/C2776107976","wikidata":"https://www.wikidata.org/wiki/Q1786433","display_name":"Tumor microenvironment","level":3,"score":0.4259999990463257},{"id":"https://openalex.org/C121608353","wikidata":"https://www.wikidata.org/wiki/Q12078","display_name":"Cancer","level":2,"score":0.4034000039100647},{"id":"https://openalex.org/C2776090121","wikidata":"https://www.wikidata.org/wiki/Q193529","display_name":"T cell","level":3,"score":0.39640000462532043},{"id":"https://openalex.org/C127561419","wikidata":"https://www.wikidata.org/wiki/Q224527","display_name":"Downregulation and upregulation","level":3,"score":0.3874000012874603},{"id":"https://openalex.org/C203014093","wikidata":"https://www.wikidata.org/wiki/Q101929","display_name":"Immunology","level":1,"score":0.3763999938964844},{"id":"https://openalex.org/C105696609","wikidata":"https://www.wikidata.org/wiki/Q1068809","display_name":"Cell cycle checkpoint","level":4,"score":0.34049999713897705},{"id":"https://openalex.org/C62478195","wikidata":"https://www.wikidata.org/wiki/Q828130","display_name":"Signal transduction","level":2,"score":0.33570000529289246},{"id":"https://openalex.org/C21705690","wikidata":"https://www.wikidata.org/wiki/Q2907609","display_name":"CTLA-4","level":4,"score":0.32409998774528503},{"id":"https://openalex.org/C136449434","wikidata":"https://www.wikidata.org/wiki/Q428253","display_name":"Innate immune system","level":3,"score":0.3206999897956848},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.31380000710487366},{"id":"https://openalex.org/C147483822","wikidata":"https://www.wikidata.org/wiki/Q103537","display_name":"Antigen","level":2,"score":0.3100999891757965},{"id":"https://openalex.org/C1491633281","wikidata":"https://www.wikidata.org/wiki/Q7868","display_name":"Cell","level":2,"score":0.3084000051021576},{"id":"https://openalex.org/C3875195","wikidata":"https://www.wikidata.org/wiki/Q5099363","display_name":"Chimeric antigen receptor","level":4,"score":0.295199990272522},{"id":"https://openalex.org/C2776256026","wikidata":"https://www.wikidata.org/wiki/Q47912","display_name":"Lung cancer","level":2,"score":0.29170000553131104},{"id":"https://openalex.org/C96232424","wikidata":"https://www.wikidata.org/wiki/Q4118072","display_name":"Cancer cell","level":3,"score":0.28780001401901245},{"id":"https://openalex.org/C31573885","wikidata":"https://www.wikidata.org/wiki/Q304484","display_name":"Programmed cell death","level":3,"score":0.2736000120639801}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.33696/cancerimmunol.7.113","doi":"https://doi.org/10.33696/cancerimmunol.7.113","is_oa":true,"landing_page_url":"https://doi.org/10.33696/cancerimmunol.7.113","pdf_url":"https://www.scientificarchives.com/public/assets/articles/article-pdf-1766229657-1610.pdf","source":{"id":"https://openalex.org/S4387278351","display_name":"Journal of Cancer Immunology","issn_l":"2689-968X","issn":["2689-968X"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core"],"host_organization":"https://openalex.org/P4323867245","host_organization_name":"Scientific Archives LLC","host_organization_lineage":["https://openalex.org/P4323867245"],"host_organization_lineage_names":["Scientific Archives LLC"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Journal of Cancer Immunology","raw_type":"journal-article"}],"best_oa_location":{"id":"doi:10.33696/cancerimmunol.7.113","doi":"https://doi.org/10.33696/cancerimmunol.7.113","is_oa":true,"landing_page_url":"https://doi.org/10.33696/cancerimmunol.7.113","pdf_url":"https://www.scientificarchives.com/public/assets/articles/article-pdf-1766229657-1610.pdf","source":{"id":"https://openalex.org/S4387278351","display_name":"Journal of Cancer Immunology","issn_l":"2689-968X","issn":["2689-968X"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core"],"host_organization":"https://openalex.org/P4323867245","host_organization_name":"Scientific Archives LLC","host_organization_lineage":["https://openalex.org/P4323867245"],"host_organization_lineage_names":["Scientific Archives LLC"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Journal of Cancer Immunology","raw_type":"journal-article"},"sustainable_development_goals":[{"id":"https://metadata.un.org/sdg/3","score":1.0,"display_name":"Good health and well-being"}],"study_designs":[],"awards":[],"funders":[],"has_content":{"pdf":true,"grobid_xml":true},"content_urls":{"pdf":"https://content.openalex.org/works/W7125597602.pdf","grobid_xml":"https://content.openalex.org/works/W7125597602.grobid-xml"},"referenced_works_count":167,"referenced_works":["https://openalex.org/W1512799118","https://openalex.org/W1572739876","https://openalex.org/W1661441964","https://openalex.org/W1913188064","https://openalex.org/W1920011500","https://openalex.org/W1982488143","https://openalex.org/W1985735048","https://openalex.org/W1987165863","https://openalex.org/W1991807494","https://openalex.org/W1999623709","https://openalex.org/W2014208459","https://openalex.org/W2018161209","https://openalex.org/W2026426963","https://openalex.org/W2029399624","https://openalex.org/W2033478138","https://openalex.org/W2033488040","https://openalex.org/W2038743671","https://openalex.org/W2039949492","https://openalex.org/W2043946720","https://openalex.org/W2046409157","https://openalex.org/W2050457398","https://openalex.org/W2058089640","https://openalex.org/W2068052762","https://openalex.org/W2070631889","https://openalex.org/W2081484203","https://openalex.org/W2092446140","https://openalex.org/W2095096783","https://openalex.org/W2097288420","https://openalex.org/W2097995306","https://openalex.org/W2101492664","https://openalex.org/W2107473879","https://openalex.org/W2107598346","https://openalex.org/W2112400160","https://openalex.org/W2114738239","https://openalex.org/W2116171543","https://openalex.org/W2117552772","https://openalex.org/W2118546263","https://openalex.org/W2118705059","https://openalex.org/W2119064369","https://openalex.org/W2122730216","https://openalex.org/W2125616358","https://openalex.org/W2132020367","https://openalex.org/W2133202774","https://openalex.org/W2133346943","https://openalex.org/W2136754957","https://openalex.org/W2137524068","https://openalex.org/W2142541925","https://openalex.org/W2142943268","https://openalex.org/W2147132132","https://openalex.org/W2147605136","https://openalex.org/W2157041114","https://openalex.org/W2166932124","https://openalex.org/W2465860350","https://openalex.org/W2526793520","https://openalex.org/W2529484692","https://openalex.org/W2537734913","https://openalex.org/W2559803603","https://openalex.org/W2587048937","https://openalex.org/W2593111137","https://openalex.org/W2596120176","https://openalex.org/W2651055861","https://openalex.org/W2655262992","https://openalex.org/W2711497375","https://openalex.org/W2743510679","https://openalex.org/W2753155927","https://openalex.org/W2765132620","https://openalex.org/W2769767397","https://openalex.org/W2781621373","https://openalex.org/W2785864157","https://openalex.org/W2792883957","https://openalex.org/W2799553179","https://openalex.org/W2885781276","https://openalex.org/W2895183267","https://openalex.org/W2900010829","https://openalex.org/W2902856530","https://openalex.org/W2903686952","https://openalex.org/W2905817704","https://openalex.org/W2906369032","https://openalex.org/W2907564726","https://openalex.org/W2910310961","https://openalex.org/W2916957847","https://openalex.org/W2918546246","https://openalex.org/W2921353943","https://openalex.org/W2924122631","https://openalex.org/W2941782360","https://openalex.org/W2945223752","https://openalex.org/W2964199936","https://openalex.org/W2979621416","https://openalex.org/W3001729162","https://openalex.org/W3003928586","https://openalex.org/W3004293125","https://openalex.org/W3006201797","https://openalex.org/W3025076282","https://openalex.org/W3029799931","https://openalex.org/W3037333252","https://openalex.org/W3041721952","https://openalex.org/W3083349647","https://openalex.org/W3087245120","https://openalex.org/W3121724392","https://openalex.org/W3124957342","https://openalex.org/W3134238388","https://openalex.org/W3136278250","https://openalex.org/W3138556548","https://openalex.org/W3138634353","https://openalex.org/W3151572223","https://openalex.org/W3157024363","https://openalex.org/W3171434019","https://openalex.org/W3177496545","https://openalex.org/W3199671843","https://openalex.org/W3201716326","https://openalex.org/W3201824706","https://openalex.org/W3203838707","https://openalex.org/W3212804507","https://openalex.org/W4205317477","https://openalex.org/W4205677074","https://openalex.org/W4206239577","https://openalex.org/W4214661080","https://openalex.org/W4220969080","https://openalex.org/W4224283600","https://openalex.org/W4229070672","https://openalex.org/W4280554695","https://openalex.org/W4280599663","https://openalex.org/W4282935821","https://openalex.org/W4307027599","https://openalex.org/W4307644364","https://openalex.org/W4308910119","https://openalex.org/W4310024016","https://openalex.org/W4319065859","https://openalex.org/W4323539126","https://openalex.org/W4353060526","https://openalex.org/W4362465890","https://openalex.org/W4365504509","https://openalex.org/W4367054559","https://openalex.org/W4367314585","https://openalex.org/W4385197413","https://openalex.org/W4385760390","https://openalex.org/W4387378477","https://openalex.org/W4389327718","https://openalex.org/W4389480350","https://openalex.org/W4390917986","https://openalex.org/W4391512597","https://openalex.org/W4392109220","https://openalex.org/W4394892953","https://openalex.org/W4399246680","https://openalex.org/W4399323228","https://openalex.org/W4399355537","https://openalex.org/W4399856128","https://openalex.org/W4401420347","https://openalex.org/W4402118699","https://openalex.org/W4404615977","https://openalex.org/W4405218689","https://openalex.org/W4406117717","https://openalex.org/W4406405667","https://openalex.org/W4407417101","https://openalex.org/W4407716534","https://openalex.org/W4407984288","https://openalex.org/W4408178378","https://openalex.org/W4408236094","https://openalex.org/W4408491186","https://openalex.org/W4408698702","https://openalex.org/W4408720461","https://openalex.org/W4409251969","https://openalex.org/W4410443553","https://openalex.org/W4410874907","https://openalex.org/W4411234684","https://openalex.org/W4411638096","https://openalex.org/W4412653705"],"related_works":["https://openalex.org/W2799553179","https://openalex.org/W7129080542","https://openalex.org/W4391749566","https://openalex.org/W3082095135","https://openalex.org/W2966128960","https://openalex.org/W4412124266","https://openalex.org/W4220972885","https://openalex.org/W3106005610","https://openalex.org/W3138556548","https://openalex.org/W4416746739"],"abstract_inverted_index":{"The":[0,96,203],"introduction":[1],"of":[2,84,114,137,205,236],"immune":[3,198],"checkpoint":[4,149,238],"inhibitors":[5],"(ICIs)":[6],"targeting":[7],"cytotoxic":[8],"T-lymphocyte\u2013associated":[9],"protein":[10,18],"4":[11],"(CTLA-4)":[12],"and":[13,63,86,117,161,170,188,196,227,240,245,249,258],"later":[14],"programmed":[15],"cell":[16,52,60,105,194],"death":[17],"1":[19],"(PD-1)":[20],"or":[21,88],"its":[22],"ligand":[23],"(PD-L1)":[24],"marked":[25],"a":[26,70,82],"turning":[27],"point":[28],"in":[29,57,73,92,109,151,210,225],"cancer":[30,152],"therapy.":[31,153],"These":[32],"agents":[33,219],"validated":[34],"the":[35,93,134,233],"principle":[36],"that":[37,48],"durable":[38],"tumor":[39,120],"control":[40],"can":[41],"be":[42],"achieved":[43],"by":[44],"releasing":[45],"inhibitory":[46],"pathways":[47,150,223],"restrain":[49],"antitumor":[50],"T":[51,104,193],"responses.":[53],"Long-term":[54],"survival":[55],"benefits":[56,78],"melanoma,":[58],"non-small":[59],"lung":[61],"cancer,":[62],"other":[64],"malignancies":[65],"have":[66,200],"established":[67],"immunotherapy":[68,260],"as":[69,157,174],"defining":[71],"development":[72],"oncology.":[74],"However,":[75],"long-term":[76],"clinical":[77,215],"remain":[79,224],"confined":[80],"to":[81,179,191],"minority":[83],"patients,":[85],"resistance":[87,243],"relapse":[89],"is":[90],"common":[91],"remaining":[94],"patients.":[95],"mechanisms":[97,244],"underlying":[98],"this":[99],"limited":[100],"efficacy":[101],"include":[102],"inadequate":[103],"infiltration,":[106],"tumor-intrinsic":[107],"defects":[108],"antigen":[110],"presentation,":[111],"compensatory":[112],"upregulation":[113],"alternative":[115],"checkpoints,":[116,166],"an":[118,207],"immunosuppressive":[119],"microenvironment":[121],"(TME).":[122],"In":[123],"addition,":[124],"immune-related":[125],"toxicities,":[126],"particularly":[127],"those":[128],"associated":[129],"with":[130,164,212],"CTLA-4":[131],"blockade,":[132],"restrict":[133],"broader":[135],"use":[136],"these":[138,142],"agents.":[139],"To":[140],"overcome":[141,192],"barriers,":[143],"attention":[144],"has":[145],"shifted":[146],"toward":[147],"next-generation":[148,237],"Inhibitory":[154],"receptors,":[155],"such":[156],"LAG-3,":[158],"TIGIT,":[159],"TIM-3,":[160],"VISTA,":[162],"along":[163],"innate":[165],"including":[167,253],"CD47-SIRP\u03b1,":[168],"NKG2A,":[169],"Siglec-15,":[171],"are":[172],"emerging":[173],"promising":[175],"targets.":[176],"Simultaneously,":[177],"strategies":[178],"enhance":[180],"co-stimulatory":[181],"signaling":[182],"through":[183],"OX40,":[184],"4-1BB,":[185],"ICOS,":[186],"GITR,":[187],"CD40":[189],"aim":[190],"exhaustion":[195],"broaden":[197],"activation":[199],"been":[201],"developed.":[202],"approval":[204],"relatlimab,":[206],"anti-LAG-3":[208],"antibody,":[209],"combination":[211],"nivolumab,":[213],"provides":[214],"proof-of-concept,":[216],"while":[217],"many":[218],"directed":[220],"at":[221],"additional":[222],"early-":[226],"late-phase":[228],"trials.":[229],"This":[230],"review":[231],"summarizes":[232],"current":[234],"knowledge":[235],"biology":[239],"development,":[241],"highlights":[242],"biomarker-driven":[246],"patient":[247],"selection,":[248],"considers":[250],"future":[251],"approaches,":[252],"multispecific":[254],"antibodies,":[255],"engineered":[256],"cytokines,":[257],"precision":[259],"strategies.":[261]},"counts_by_year":[{"year":2026,"cited_by_count":4}],"updated_date":"2026-10-28T10:33:24.094632","created_date":"2026-01-25T00:00:00"}