Comprehensive analysis of fibroblast activation protein expression across 23 tumor indications: insights for biomarker development in cancer immunotherapies
IntroductionFibroblast activation protein (FAP) is predominantly upregulated in various tumor microenvironments and scarcely expressed in normal tissues.MethodsWe analyzed FAP across 1216 tissue samples covering 23 tumor types and 70 subtypes.ResultsElevated FAP levels were notable in breast, pancre...
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| Format: | Article |
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Frontiers Media S.A.
2024-03-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1352615/full |
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| author | Sebastian Dziadek Anton Kraxner Wei-Yi Cheng Tai-Hsien Ou Yang Mike Flores Noah Theiss Tsu-Shuen Tsao Emilia Andersson Suzana Vega Harring Ann-Marie E. Bröske Maurizio Ceppi Volker Teichgräber Jehad Charo |
| author_facet | Sebastian Dziadek Anton Kraxner Wei-Yi Cheng Tai-Hsien Ou Yang Mike Flores Noah Theiss Tsu-Shuen Tsao Emilia Andersson Suzana Vega Harring Ann-Marie E. Bröske Maurizio Ceppi Volker Teichgräber Jehad Charo |
| author_sort | Sebastian Dziadek |
| collection | DOAJ |
| description | IntroductionFibroblast activation protein (FAP) is predominantly upregulated in various tumor microenvironments and scarcely expressed in normal tissues.MethodsWe analyzed FAP across 1216 tissue samples covering 23 tumor types and 70 subtypes.ResultsElevated FAP levels were notable in breast, pancreatic, esophageal, and lung cancers. Using immunohistochemistry and RNAseq, a correlation between FAP gene and protein expression was found. Evaluating FAP’s clinical significance, we assessed 29 cohorts from 12 clinical trials, including both mono and combination therapies with the PD-L1 inhibitor atezolizumab and chemotherapy. A trend links higher FAP expression to poorer prognosis, particularly in RCC, across both treatment arms. However, four cohorts showed improved survival with high FAP, while in four others, FAP had no apparent survival impact.ConclusionsOur results emphasize FAP’s multifaceted role in therapy response, suggesting its potential as a cancer immunotherapy biomarker. |
| first_indexed | 2024-04-24T23:48:23Z |
| format | Article |
| id | doaj.art-1d302b244ca44580b4d610b776267f3e |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-24T23:48:23Z |
| publishDate | 2024-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-1d302b244ca44580b4d610b776267f3e2024-03-15T04:31:11ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-03-011510.3389/fimmu.2024.13526151352615Comprehensive analysis of fibroblast activation protein expression across 23 tumor indications: insights for biomarker development in cancer immunotherapiesSebastian Dziadek0Anton Kraxner1Wei-Yi Cheng2Tai-Hsien Ou Yang3Mike Flores4Noah Theiss5Tsu-Shuen Tsao6Emilia Andersson7Suzana Vega Harring8Ann-Marie E. Bröske9Maurizio Ceppi10Volker Teichgräber11Jehad Charo12Roche Pharma Research and Early Development, Oncology, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd., Basel, SwitzerlandRoche Pharma Research and Early Development, Oncology, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd., Basel, SwitzerlandRoche Pharma Research and Early Development, Data and Analytics, Roche Translational & Clinical Research Center, F. Hoffmann-La Roche Ltd, Little Falls, NJ, United StatesRoche Pharma Research and Early Development, Data and Analytics, Roche Translational & Clinical Research Center, F. Hoffmann-La Roche Ltd, Little Falls, NJ, United StatesRoche Tissue Diagnostics, Tucson, AZ, United StatesRoche Tissue Diagnostics, Tucson, AZ, United StatesRoche Tissue Diagnostics, Tucson, AZ, United StatesRoche Pharma Research and Early Development, Oncology, Roche Innovation Center Munich, Roche Diagnostics GmbH, Penzberg, GermanyRoche Pharma Research and Early Development, Oncology, Roche Innovation Center Munich, Roche Diagnostics GmbH, Penzberg, GermanyRoche Pharma Research and Early Development, Oncology, Roche Innovation Center Munich, Roche Diagnostics GmbH, Penzberg, GermanyRoche Pharma Research and Early Development, Oncology, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd., Basel, SwitzerlandRoche Pharma Research and Early Development, Oncology, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd., Basel, SwitzerlandRoche Pharma Research and Early Development, Oncology, Roche Innovation Center Zurich, Roche Glycart AG, Schlieren, SwitzerlandIntroductionFibroblast activation protein (FAP) is predominantly upregulated in various tumor microenvironments and scarcely expressed in normal tissues.MethodsWe analyzed FAP across 1216 tissue samples covering 23 tumor types and 70 subtypes.ResultsElevated FAP levels were notable in breast, pancreatic, esophageal, and lung cancers. Using immunohistochemistry and RNAseq, a correlation between FAP gene and protein expression was found. Evaluating FAP’s clinical significance, we assessed 29 cohorts from 12 clinical trials, including both mono and combination therapies with the PD-L1 inhibitor atezolizumab and chemotherapy. A trend links higher FAP expression to poorer prognosis, particularly in RCC, across both treatment arms. However, four cohorts showed improved survival with high FAP, while in four others, FAP had no apparent survival impact.ConclusionsOur results emphasize FAP’s multifaceted role in therapy response, suggesting its potential as a cancer immunotherapy biomarker.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1352615/fullfibroblast activation proteinimmunohistochemistrymRNA expressionimmunotherapyclinical outcomes |
| spellingShingle | Sebastian Dziadek Anton Kraxner Wei-Yi Cheng Tai-Hsien Ou Yang Mike Flores Noah Theiss Tsu-Shuen Tsao Emilia Andersson Suzana Vega Harring Ann-Marie E. Bröske Maurizio Ceppi Volker Teichgräber Jehad Charo Comprehensive analysis of fibroblast activation protein expression across 23 tumor indications: insights for biomarker development in cancer immunotherapies Frontiers in Immunology fibroblast activation protein immunohistochemistry mRNA expression immunotherapy clinical outcomes |
| title | Comprehensive analysis of fibroblast activation protein expression across 23 tumor indications: insights for biomarker development in cancer immunotherapies |
| title_full | Comprehensive analysis of fibroblast activation protein expression across 23 tumor indications: insights for biomarker development in cancer immunotherapies |
| title_fullStr | Comprehensive analysis of fibroblast activation protein expression across 23 tumor indications: insights for biomarker development in cancer immunotherapies |
| title_full_unstemmed | Comprehensive analysis of fibroblast activation protein expression across 23 tumor indications: insights for biomarker development in cancer immunotherapies |
| title_short | Comprehensive analysis of fibroblast activation protein expression across 23 tumor indications: insights for biomarker development in cancer immunotherapies |
| title_sort | comprehensive analysis of fibroblast activation protein expression across 23 tumor indications insights for biomarker development in cancer immunotherapies |
| topic | fibroblast activation protein immunohistochemistry mRNA expression immunotherapy clinical outcomes |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1352615/full |
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