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Immunosurveillance shapes the emergence of neo-epitope landscapes of sarcomas, revealing prime targets for immunotherapy
T cells recognize tumor-derived mutated peptides presented on MHC by tumors. The recognition of these neo-epitopes leads to rejection of tumors, an event that is critical for successful cancer immunosurveillance. Determination of tumor-rejecting neo-epitopes in human tumors has proved difficult, tho...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Clinical Investigation
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10371341/ https://www.ncbi.nlm.nih.gov/pubmed/37427594 http://dx.doi.org/10.1172/jci.insight.170324 |
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author | Osei-Hwedieh, David O. Sedlacek, Abigail L. Hernandez, Luis Mena Yamoah, Archibald Agyekum Iyer, Swati G. Weiss, Kurt R. Binder, Robert J. |
author_facet | Osei-Hwedieh, David O. Sedlacek, Abigail L. Hernandez, Luis Mena Yamoah, Archibald Agyekum Iyer, Swati G. Weiss, Kurt R. Binder, Robert J. |
author_sort | Osei-Hwedieh, David O. |
collection | PubMed |
description | T cells recognize tumor-derived mutated peptides presented on MHC by tumors. The recognition of these neo-epitopes leads to rejection of tumors, an event that is critical for successful cancer immunosurveillance. Determination of tumor-rejecting neo-epitopes in human tumors has proved difficult, though recently developed systems approaches are becoming increasingly useful at evaluating their immunogenicity. We have used the differential aggretope index to determine the neo-epitope burden of sarcomas and observed a conspicuously titrated antigenic landscape, ranging from the highly antigenic osteosarcomas to the low antigenic leiomyosarcomas and liposarcomas. We showed that the antigenic landscape of the tumors inversely reflected the historical T cell responses in the tumor-bearing patients. We predicted that highly antigenic tumors with poor antitumor T cell responses, such as osteosarcomas, would be responsive to T cell–based immunotherapy regimens and demonstrated this in a murine osteosarcoma model. Our study presents a potentially novel pipeline for determining antigenicity of human tumors, provides an accurate predictor of potential neo-epitopes, and will be an important indicator of which cancers to target with T cell–enhancing immunotherapy. |
format | Online Article Text |
id | pubmed-10371341 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | American Society for Clinical Investigation |
record_format | MEDLINE/PubMed |
spelling | pubmed-103713412023-07-27 Immunosurveillance shapes the emergence of neo-epitope landscapes of sarcomas, revealing prime targets for immunotherapy Osei-Hwedieh, David O. Sedlacek, Abigail L. Hernandez, Luis Mena Yamoah, Archibald Agyekum Iyer, Swati G. Weiss, Kurt R. Binder, Robert J. JCI Insight Research Article T cells recognize tumor-derived mutated peptides presented on MHC by tumors. The recognition of these neo-epitopes leads to rejection of tumors, an event that is critical for successful cancer immunosurveillance. Determination of tumor-rejecting neo-epitopes in human tumors has proved difficult, though recently developed systems approaches are becoming increasingly useful at evaluating their immunogenicity. We have used the differential aggretope index to determine the neo-epitope burden of sarcomas and observed a conspicuously titrated antigenic landscape, ranging from the highly antigenic osteosarcomas to the low antigenic leiomyosarcomas and liposarcomas. We showed that the antigenic landscape of the tumors inversely reflected the historical T cell responses in the tumor-bearing patients. We predicted that highly antigenic tumors with poor antitumor T cell responses, such as osteosarcomas, would be responsive to T cell–based immunotherapy regimens and demonstrated this in a murine osteosarcoma model. Our study presents a potentially novel pipeline for determining antigenicity of human tumors, provides an accurate predictor of potential neo-epitopes, and will be an important indicator of which cancers to target with T cell–enhancing immunotherapy. American Society for Clinical Investigation 2023-07-10 /pmc/articles/PMC10371341/ /pubmed/37427594 http://dx.doi.org/10.1172/jci.insight.170324 Text en © 2023 Osei-Hwedieh et al. https://creativecommons.org/licenses/by/4.0/This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Research Article Osei-Hwedieh, David O. Sedlacek, Abigail L. Hernandez, Luis Mena Yamoah, Archibald Agyekum Iyer, Swati G. Weiss, Kurt R. Binder, Robert J. Immunosurveillance shapes the emergence of neo-epitope landscapes of sarcomas, revealing prime targets for immunotherapy |
title | Immunosurveillance shapes the emergence of neo-epitope landscapes of sarcomas, revealing prime targets for immunotherapy |
title_full | Immunosurveillance shapes the emergence of neo-epitope landscapes of sarcomas, revealing prime targets for immunotherapy |
title_fullStr | Immunosurveillance shapes the emergence of neo-epitope landscapes of sarcomas, revealing prime targets for immunotherapy |
title_full_unstemmed | Immunosurveillance shapes the emergence of neo-epitope landscapes of sarcomas, revealing prime targets for immunotherapy |
title_short | Immunosurveillance shapes the emergence of neo-epitope landscapes of sarcomas, revealing prime targets for immunotherapy |
title_sort | immunosurveillance shapes the emergence of neo-epitope landscapes of sarcomas, revealing prime targets for immunotherapy |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10371341/ https://www.ncbi.nlm.nih.gov/pubmed/37427594 http://dx.doi.org/10.1172/jci.insight.170324 |
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