Lacking Immunotherapy Biomarkers for Biliary Tract Cancer: A Comprehensive Systematic Literature Review and Meta-Analysis
Background: Immunotherapy has recently been incorporated into the spectrum of biliary tract cancer (BTC) treatment. The identification of predictive response biomarkers is essential in order to identify those patients who may benefit most from this novel treatment option. Here, we propose a systemat...
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MDPI AG
2023-08-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/12/16/2098 |
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| author | Giorgio Frega Fernando P. Cossio Jesus M. Banales Vincenzo Cardinale Rocio I. R. Macias Chiara Braconi Angela Lamarca |
| author_facet | Giorgio Frega Fernando P. Cossio Jesus M. Banales Vincenzo Cardinale Rocio I. R. Macias Chiara Braconi Angela Lamarca |
| author_sort | Giorgio Frega |
| collection | DOAJ |
| description | Background: Immunotherapy has recently been incorporated into the spectrum of biliary tract cancer (BTC) treatment. The identification of predictive response biomarkers is essential in order to identify those patients who may benefit most from this novel treatment option. Here, we propose a systematic literature review and a meta-analysis of PD-1, PD-L1, and other immune-related biomarker expression levels in patients with BTC. Methods: Prisma guidelines were followed for this systematic review and meta-analysis. Eligible studies were searched on PubMed. Studies published between 2017 and 2022, reporting data on PD-1/PD-L1 expression and other immune-related biomarkers in patients with BTC, were considered eligible. Results: A total of 61 eligible studies were identified. Despite the great heterogeneity between 39 studies reporting data on PD-L1 expression, we found a mean PD-L1 expression percentage (by choosing the lowest cut-off per study) of 25.6% (95% CI 21.0 to 30.3) in BTCs. The mean expression percentages of PD-L1 were 27.3%, 21.3%, and 27.4% in intrahepatic cholangiocarcinomas (iCCAs—15 studies), perihilar–distal CCAs (p/dCCAs—7 studies), and gallbladder cancer (GBC—5 studies), respectively. Furthermore, 4.6% (95% CI 2.38 to 6.97) and 2.5% (95% CI 1.75 to 3.34) of BTCs could be classified as TMB-H and MSI/MMRd tumors, respectively. Conclusion: From our analysis, PD-L1 expression was found to occur approximately in 26% of BTC patients, with minimal differences based on anatomical location. TMB-H and MSI molecular phenotypes occurred less frequently. We still lack a reliable biomarker, especially in patients with mismatch-proficient tumors, and we must need to make an effort to conceive new prospective biomarker discovery studies. |
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| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-11T00:02:34Z |
| publishDate | 2023-08-01 |
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| series | Cells |
| spelling | doaj.art-a27456594e9c46b1b086f68ea1e603942023-11-19T00:37:29ZengMDPI AGCells2073-44092023-08-011216209810.3390/cells12162098Lacking Immunotherapy Biomarkers for Biliary Tract Cancer: A Comprehensive Systematic Literature Review and Meta-AnalysisGiorgio Frega0Fernando P. Cossio1Jesus M. Banales2Vincenzo Cardinale3Rocio I. R. Macias4Chiara Braconi5Angela Lamarca6Osteoncology, Soft Tissue and Bone Sarcomas, Innovative Therapy Unit, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, ItalyDepartment of Organic Chemistry I, Center of Innovation in Advanced Chemistry (ORFEO-CINQA), University of the Basque Country/Euskal Herriko Unibertsitatea (UPV/EHU), Donostia International Physics Center (DIPC), 48940 Donostia-San Sebastian, SpainDepartment of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute—Donostia University Hospital, University of the Basque Country (UPV/EHU), Ikerbasque, 48940 San Sebastian, SpainDepartment of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, 00185 Rome, ItalyNational Institute for the Study of Liver and Gastrointestinal Diseases (CIBERehd), Instituto de Salud Carlos III, 28029 Madrid, SpainSchool of Cancer Sciences, University of Glasgow, Glasgow G12 8QQ, UKDepartment of Oncology—OncoHealth Institute, Instituto de Investigación Sanitaria de la Fundación Jiménez Díaz, Fundación Jiménez Díaz University Hospital, 28040 Madrid, SpainBackground: Immunotherapy has recently been incorporated into the spectrum of biliary tract cancer (BTC) treatment. The identification of predictive response biomarkers is essential in order to identify those patients who may benefit most from this novel treatment option. Here, we propose a systematic literature review and a meta-analysis of PD-1, PD-L1, and other immune-related biomarker expression levels in patients with BTC. Methods: Prisma guidelines were followed for this systematic review and meta-analysis. Eligible studies were searched on PubMed. Studies published between 2017 and 2022, reporting data on PD-1/PD-L1 expression and other immune-related biomarkers in patients with BTC, were considered eligible. Results: A total of 61 eligible studies were identified. Despite the great heterogeneity between 39 studies reporting data on PD-L1 expression, we found a mean PD-L1 expression percentage (by choosing the lowest cut-off per study) of 25.6% (95% CI 21.0 to 30.3) in BTCs. The mean expression percentages of PD-L1 were 27.3%, 21.3%, and 27.4% in intrahepatic cholangiocarcinomas (iCCAs—15 studies), perihilar–distal CCAs (p/dCCAs—7 studies), and gallbladder cancer (GBC—5 studies), respectively. Furthermore, 4.6% (95% CI 2.38 to 6.97) and 2.5% (95% CI 1.75 to 3.34) of BTCs could be classified as TMB-H and MSI/MMRd tumors, respectively. Conclusion: From our analysis, PD-L1 expression was found to occur approximately in 26% of BTC patients, with minimal differences based on anatomical location. TMB-H and MSI molecular phenotypes occurred less frequently. We still lack a reliable biomarker, especially in patients with mismatch-proficient tumors, and we must need to make an effort to conceive new prospective biomarker discovery studies.https://www.mdpi.com/2073-4409/12/16/2098biliary cancerimmunotherapypredictive biomarkers |
| spellingShingle | Giorgio Frega Fernando P. Cossio Jesus M. Banales Vincenzo Cardinale Rocio I. R. Macias Chiara Braconi Angela Lamarca Lacking Immunotherapy Biomarkers for Biliary Tract Cancer: A Comprehensive Systematic Literature Review and Meta-Analysis Cells biliary cancer immunotherapy predictive biomarkers |
| title | Lacking Immunotherapy Biomarkers for Biliary Tract Cancer: A Comprehensive Systematic Literature Review and Meta-Analysis |
| title_full | Lacking Immunotherapy Biomarkers for Biliary Tract Cancer: A Comprehensive Systematic Literature Review and Meta-Analysis |
| title_fullStr | Lacking Immunotherapy Biomarkers for Biliary Tract Cancer: A Comprehensive Systematic Literature Review and Meta-Analysis |
| title_full_unstemmed | Lacking Immunotherapy Biomarkers for Biliary Tract Cancer: A Comprehensive Systematic Literature Review and Meta-Analysis |
| title_short | Lacking Immunotherapy Biomarkers for Biliary Tract Cancer: A Comprehensive Systematic Literature Review and Meta-Analysis |
| title_sort | lacking immunotherapy biomarkers for biliary tract cancer a comprehensive systematic literature review and meta analysis |
| topic | biliary cancer immunotherapy predictive biomarkers |
| url | https://www.mdpi.com/2073-4409/12/16/2098 |
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