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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...

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Autores principales: Osei-Hwedieh, David O., Sedlacek, Abigail L., Hernandez, Luis Mena, Yamoah, Archibald Agyekum, Iyer, Swati G., Weiss, Kurt R., Binder, Robert J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Clinical Investigation 2023
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.
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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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