Mutated processes predict immune checkpoint inhibitor therapy benefit in metastatic melanoma
Abstract Immune Checkpoint Inhibitor (ICI) therapy has revolutionized treatment for advanced melanoma; however, only a subset of patients benefit from this treatment. Despite considerable efforts, the Tumor Mutation Burden (TMB) is the only FDA-approved biomarker in melanoma. However, the mechanisms...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2022-09-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-022-32838-4 |
| _version_ | 1797675235959373824 |
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| author | Andrew Patterson Noam Auslander |
| author_facet | Andrew Patterson Noam Auslander |
| author_sort | Andrew Patterson |
| collection | DOAJ |
| description | Abstract Immune Checkpoint Inhibitor (ICI) therapy has revolutionized treatment for advanced melanoma; however, only a subset of patients benefit from this treatment. Despite considerable efforts, the Tumor Mutation Burden (TMB) is the only FDA-approved biomarker in melanoma. However, the mechanisms underlying TMB association with prolonged ICI survival are not entirely understood and may depend on numerous confounding factors. To identify more interpretable ICI response biomarkers based on tumor mutations, we train classifiers using mutations within distinct biological processes. We evaluate a variety of feature selection and classification methods and identify key mutated biological processes that provide improved predictive capability compared to the TMB. The top mutated processes we identify are leukocyte and T-cell proliferation regulation, which demonstrate stable predictive performance across different data cohorts of melanoma patients treated with ICI. This study provides biologically interpretable genomic predictors of ICI response with substantially improved predictive performance over the TMB. |
| first_indexed | 2024-03-11T22:11:54Z |
| format | Article |
| id | doaj.art-5662e31a867b4327a602d4e21ccd8dcb |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-11T22:11:54Z |
| publishDate | 2022-09-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-5662e31a867b4327a602d4e21ccd8dcb2023-09-24T11:23:27ZengNature PortfolioNature Communications2041-17232022-09-0113111010.1038/s41467-022-32838-4Mutated processes predict immune checkpoint inhibitor therapy benefit in metastatic melanomaAndrew Patterson0Noam Auslander1Genomics and Computational Biology Graduate Group, University of Pennsylvania - Perelman School of MedicineProgram in Molecular and Cellular Oncogenesis, The Wistar InstituteAbstract Immune Checkpoint Inhibitor (ICI) therapy has revolutionized treatment for advanced melanoma; however, only a subset of patients benefit from this treatment. Despite considerable efforts, the Tumor Mutation Burden (TMB) is the only FDA-approved biomarker in melanoma. However, the mechanisms underlying TMB association with prolonged ICI survival are not entirely understood and may depend on numerous confounding factors. To identify more interpretable ICI response biomarkers based on tumor mutations, we train classifiers using mutations within distinct biological processes. We evaluate a variety of feature selection and classification methods and identify key mutated biological processes that provide improved predictive capability compared to the TMB. The top mutated processes we identify are leukocyte and T-cell proliferation regulation, which demonstrate stable predictive performance across different data cohorts of melanoma patients treated with ICI. This study provides biologically interpretable genomic predictors of ICI response with substantially improved predictive performance over the TMB.https://doi.org/10.1038/s41467-022-32838-4 |
| spellingShingle | Andrew Patterson Noam Auslander Mutated processes predict immune checkpoint inhibitor therapy benefit in metastatic melanoma Nature Communications |
| title | Mutated processes predict immune checkpoint inhibitor therapy benefit in metastatic melanoma |
| title_full | Mutated processes predict immune checkpoint inhibitor therapy benefit in metastatic melanoma |
| title_fullStr | Mutated processes predict immune checkpoint inhibitor therapy benefit in metastatic melanoma |
| title_full_unstemmed | Mutated processes predict immune checkpoint inhibitor therapy benefit in metastatic melanoma |
| title_short | Mutated processes predict immune checkpoint inhibitor therapy benefit in metastatic melanoma |
| title_sort | mutated processes predict immune checkpoint inhibitor therapy benefit in metastatic melanoma |
| url | https://doi.org/10.1038/s41467-022-32838-4 |
| work_keys_str_mv | AT andrewpatterson mutatedprocessespredictimmunecheckpointinhibitortherapybenefitinmetastaticmelanoma AT noamauslander mutatedprocessespredictimmunecheckpointinhibitortherapybenefitinmetastaticmelanoma |