The Origin and Immune Recognition of Tumor-Specific Antigens
The dominant paradigm holds that spontaneous and therapeutically induced anti-tumor responses are mediated mainly by CD8 T cells and directed against tumor-specific antigens (TSAs). The presence of specific TSAs on cancer cells can only be proven by mass spectrometry analyses. Bioinformatic predicti...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-09-01
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| Series: | Cancers |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2072-6694/12/9/2607 |
| _version_ | 1797553838268350464 |
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| author | Anca Apavaloaei Marie-Pierre Hardy Pierre Thibault Claude Perreault |
| author_facet | Anca Apavaloaei Marie-Pierre Hardy Pierre Thibault Claude Perreault |
| author_sort | Anca Apavaloaei |
| collection | DOAJ |
| description | The dominant paradigm holds that spontaneous and therapeutically induced anti-tumor responses are mediated mainly by CD8 T cells and directed against tumor-specific antigens (TSAs). The presence of specific TSAs on cancer cells can only be proven by mass spectrometry analyses. Bioinformatic predictions and reverse immunology studies cannot provide this type of conclusive evidence. Most TSAs are coded by unmutated non-canonical transcripts that arise from cancer-specific epigenetic and splicing aberrations. When searching for TSAs, it is therefore important to perform mass spectrometry analyses that interrogate not only the canonical reading frame of annotated exome but all reading frames of the entire translatome. The majority of aberrantly expressed TSAs (aeTSAs) derive from unstable short-lived proteins that are good substrates for direct major histocompatibility complex (MHC) I presentation but poor substrates for cross-presentation. This is an important caveat, because cancer cells are poor antigen-presenting cells, and the immune system, therefore, depends on cross-presentation by dendritic cells (DCs) to detect the presence of TSAs. We, therefore, postulate that, in the untreated host, most aeTSAs are undetected by the immune system. We present evidence suggesting that vaccines inducing direct aeTSA presentation by DCs may represent an attractive strategy for cancer treatment. |
| first_indexed | 2024-03-10T16:22:19Z |
| format | Article |
| id | doaj.art-33307506ed074f23b2ec6655c0084f2d |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T16:22:19Z |
| publishDate | 2020-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-33307506ed074f23b2ec6655c0084f2d2023-11-20T13:30:22ZengMDPI AGCancers2072-66942020-09-01129260710.3390/cancers12092607The Origin and Immune Recognition of Tumor-Specific AntigensAnca Apavaloaei0Marie-Pierre Hardy1Pierre Thibault2Claude Perreault3Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, QC H3T 1J4, CanadaInstitute for Research in Immunology and Cancer, Université de Montréal, Montréal, QC H3T 1J4, CanadaInstitute for Research in Immunology and Cancer, Université de Montréal, Montréal, QC H3T 1J4, CanadaInstitute for Research in Immunology and Cancer, Université de Montréal, Montréal, QC H3T 1J4, CanadaThe dominant paradigm holds that spontaneous and therapeutically induced anti-tumor responses are mediated mainly by CD8 T cells and directed against tumor-specific antigens (TSAs). The presence of specific TSAs on cancer cells can only be proven by mass spectrometry analyses. Bioinformatic predictions and reverse immunology studies cannot provide this type of conclusive evidence. Most TSAs are coded by unmutated non-canonical transcripts that arise from cancer-specific epigenetic and splicing aberrations. When searching for TSAs, it is therefore important to perform mass spectrometry analyses that interrogate not only the canonical reading frame of annotated exome but all reading frames of the entire translatome. The majority of aberrantly expressed TSAs (aeTSAs) derive from unstable short-lived proteins that are good substrates for direct major histocompatibility complex (MHC) I presentation but poor substrates for cross-presentation. This is an important caveat, because cancer cells are poor antigen-presenting cells, and the immune system, therefore, depends on cross-presentation by dendritic cells (DCs) to detect the presence of TSAs. We, therefore, postulate that, in the untreated host, most aeTSAs are undetected by the immune system. We present evidence suggesting that vaccines inducing direct aeTSA presentation by DCs may represent an attractive strategy for cancer treatment.https://www.mdpi.com/2072-6694/12/9/2607antigen processing and presentationcancer immunotherapycross-primingimmunogenicitymajor histocompatibility complexT lymphocyte |
| spellingShingle | Anca Apavaloaei Marie-Pierre Hardy Pierre Thibault Claude Perreault The Origin and Immune Recognition of Tumor-Specific Antigens Cancers antigen processing and presentation cancer immunotherapy cross-priming immunogenicity major histocompatibility complex T lymphocyte |
| title | The Origin and Immune Recognition of Tumor-Specific Antigens |
| title_full | The Origin and Immune Recognition of Tumor-Specific Antigens |
| title_fullStr | The Origin and Immune Recognition of Tumor-Specific Antigens |
| title_full_unstemmed | The Origin and Immune Recognition of Tumor-Specific Antigens |
| title_short | The Origin and Immune Recognition of Tumor-Specific Antigens |
| title_sort | origin and immune recognition of tumor specific antigens |
| topic | antigen processing and presentation cancer immunotherapy cross-priming immunogenicity major histocompatibility complex T lymphocyte |
| url | https://www.mdpi.com/2072-6694/12/9/2607 |
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