The Immunogenic Potential of Recurrent Cancer Drug Resistance Mutations: An In Silico Study
Cancer somatic mutations have been identified as a source of antigens that can be targeted by cancer immunotherapy. In this work, expanding on previous studies, we analyze the HLA-presentation properties of mutations that are known to drive resistance to cancer targeted-therapies. We survey a large...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-10-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2020.524968/full |
| _version_ | 1828878658674098176 |
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| author | Marco Punta Victoria A. Jennings Victoria A. Jennings Alan A. Melcher Stefano Lise |
| author_facet | Marco Punta Victoria A. Jennings Victoria A. Jennings Alan A. Melcher Stefano Lise |
| author_sort | Marco Punta |
| collection | DOAJ |
| description | Cancer somatic mutations have been identified as a source of antigens that can be targeted by cancer immunotherapy. In this work, expanding on previous studies, we analyze the HLA-presentation properties of mutations that are known to drive resistance to cancer targeted-therapies. We survey a large dataset of mutations that confer resistance to different drugs and occur in numerous genes and tumor types. We show that a significant number of them are predicted in silico to be potentially immunogenic across a large proportion of the human population. Further, by analyzing a cohort of patients carrying a small subset of these resistance mutations, we provide evidence that what is observed in the general population may be indicative of the mutations’ immunogenic potential in resistant patients. Two of the mutations in our dataset had previously been experimentally validated by others and it was confirmed that some of their associated neopeptides elicit T-cell responses in vitro. The identification of potent cancer-specific antigens can be instrumental for developing more effective immunotherapies. In this work, we propose a novel list of drug-resistance mutations, several of which are recurrent, that could be of particular interest in the context of off-the-shelf precision immunotherapies such as therapeutic cancer vaccines. |
| first_indexed | 2024-12-13T09:10:04Z |
| format | Article |
| id | doaj.art-3d9fe4afd99d457c813614c55171e8f7 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-13T09:10:04Z |
| publishDate | 2020-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-3d9fe4afd99d457c813614c55171e8f72022-12-21T23:52:57ZengFrontiers Media S.A.Frontiers in Immunology1664-32242020-10-011110.3389/fimmu.2020.524968524968The Immunogenic Potential of Recurrent Cancer Drug Resistance Mutations: An In Silico StudyMarco Punta0Victoria A. Jennings1Victoria A. Jennings2Alan A. Melcher3Stefano Lise4Centre for Evolution and Cancer, The Institute of Cancer Research, London, United KingdomDepartment of Immunity and Infection, Leeds Institute of Medical Research, Leeds, United KingdomDivision of Radiotherapy and Imaging, The Institute of Cancer Research, London, United KingdomDivision of Radiotherapy and Imaging, The Institute of Cancer Research, London, United KingdomCentre for Evolution and Cancer, The Institute of Cancer Research, London, United KingdomCancer somatic mutations have been identified as a source of antigens that can be targeted by cancer immunotherapy. In this work, expanding on previous studies, we analyze the HLA-presentation properties of mutations that are known to drive resistance to cancer targeted-therapies. We survey a large dataset of mutations that confer resistance to different drugs and occur in numerous genes and tumor types. We show that a significant number of them are predicted in silico to be potentially immunogenic across a large proportion of the human population. Further, by analyzing a cohort of patients carrying a small subset of these resistance mutations, we provide evidence that what is observed in the general population may be indicative of the mutations’ immunogenic potential in resistant patients. Two of the mutations in our dataset had previously been experimentally validated by others and it was confirmed that some of their associated neopeptides elicit T-cell responses in vitro. The identification of potent cancer-specific antigens can be instrumental for developing more effective immunotherapies. In this work, we propose a novel list of drug-resistance mutations, several of which are recurrent, that could be of particular interest in the context of off-the-shelf precision immunotherapies such as therapeutic cancer vaccines.https://www.frontiersin.org/article/10.3389/fimmu.2020.524968/fullimmunogenomicscancer vaccinescancer targeted therapytumor neoantigen predictionsdrug resistanceresistance mutations |
| spellingShingle | Marco Punta Victoria A. Jennings Victoria A. Jennings Alan A. Melcher Stefano Lise The Immunogenic Potential of Recurrent Cancer Drug Resistance Mutations: An In Silico Study Frontiers in Immunology immunogenomics cancer vaccines cancer targeted therapy tumor neoantigen predictions drug resistance resistance mutations |
| title | The Immunogenic Potential of Recurrent Cancer Drug Resistance Mutations: An In Silico Study |
| title_full | The Immunogenic Potential of Recurrent Cancer Drug Resistance Mutations: An In Silico Study |
| title_fullStr | The Immunogenic Potential of Recurrent Cancer Drug Resistance Mutations: An In Silico Study |
| title_full_unstemmed | The Immunogenic Potential of Recurrent Cancer Drug Resistance Mutations: An In Silico Study |
| title_short | The Immunogenic Potential of Recurrent Cancer Drug Resistance Mutations: An In Silico Study |
| title_sort | immunogenic potential of recurrent cancer drug resistance mutations an in silico study |
| topic | immunogenomics cancer vaccines cancer targeted therapy tumor neoantigen predictions drug resistance resistance mutations |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2020.524968/full |
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