Cargando…
Membrane-localized neoantigens predict the efficacy of cancer immunotherapy
Immune checkpoint immunotherapy (ICI) can re-activate immune reactions against neoantigens, leading to remarkable remission in cancer patients. Nevertheless, only a minority of patients are responsive to ICI, and approaches for prediction of responsiveness are needed to improve the success of cancer...
Autores principales: | , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10439248/ https://www.ncbi.nlm.nih.gov/pubmed/37552990 http://dx.doi.org/10.1016/j.xcrm.2023.101145 |
_version_ | 1785092906019717120 |
---|---|
author | Goldberger, Zoe Hauert, Sylvie Chang, Kevin Kurtanich, Trevin Alpar, Aaron T. Repond, Grégoire Wang, Yue Gomes, Suzana Krishnakumar, Raga Siddarth, Prabha Swartz, Melody A. Hubbell, Jeffrey A. Briquez, Priscilla S. |
author_facet | Goldberger, Zoe Hauert, Sylvie Chang, Kevin Kurtanich, Trevin Alpar, Aaron T. Repond, Grégoire Wang, Yue Gomes, Suzana Krishnakumar, Raga Siddarth, Prabha Swartz, Melody A. Hubbell, Jeffrey A. Briquez, Priscilla S. |
author_sort | Goldberger, Zoe |
collection | PubMed |
description | Immune checkpoint immunotherapy (ICI) can re-activate immune reactions against neoantigens, leading to remarkable remission in cancer patients. Nevertheless, only a minority of patients are responsive to ICI, and approaches for prediction of responsiveness are needed to improve the success of cancer treatments. While the tumor mutational burden (TMB) correlates positively with responsiveness and survival of patients undergoing ICI, the influence of the subcellular localizations of the neoantigens remains unclear. Here, we demonstrate in both a mouse melanoma model and human clinical datasets of 1,722 ICI-treated patients that a high proportion of membrane-localized neoantigens, particularly at the plasma membrane, correlate with responsiveness to ICI therapy and improved overall survival across multiple cancer types. We further show that combining membrane localization and TMB analyses can enhance the predictability of cancer patient response to ICI. Our results may have important implications for establishing future clinical guidelines to direct the choice of treatment toward ICI. |
format | Online Article Text |
id | pubmed-10439248 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-104392482023-08-20 Membrane-localized neoantigens predict the efficacy of cancer immunotherapy Goldberger, Zoe Hauert, Sylvie Chang, Kevin Kurtanich, Trevin Alpar, Aaron T. Repond, Grégoire Wang, Yue Gomes, Suzana Krishnakumar, Raga Siddarth, Prabha Swartz, Melody A. Hubbell, Jeffrey A. Briquez, Priscilla S. Cell Rep Med Article Immune checkpoint immunotherapy (ICI) can re-activate immune reactions against neoantigens, leading to remarkable remission in cancer patients. Nevertheless, only a minority of patients are responsive to ICI, and approaches for prediction of responsiveness are needed to improve the success of cancer treatments. While the tumor mutational burden (TMB) correlates positively with responsiveness and survival of patients undergoing ICI, the influence of the subcellular localizations of the neoantigens remains unclear. Here, we demonstrate in both a mouse melanoma model and human clinical datasets of 1,722 ICI-treated patients that a high proportion of membrane-localized neoantigens, particularly at the plasma membrane, correlate with responsiveness to ICI therapy and improved overall survival across multiple cancer types. We further show that combining membrane localization and TMB analyses can enhance the predictability of cancer patient response to ICI. Our results may have important implications for establishing future clinical guidelines to direct the choice of treatment toward ICI. Elsevier 2023-08-07 /pmc/articles/PMC10439248/ /pubmed/37552990 http://dx.doi.org/10.1016/j.xcrm.2023.101145 Text en © 2023 The Author(s) https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Article Goldberger, Zoe Hauert, Sylvie Chang, Kevin Kurtanich, Trevin Alpar, Aaron T. Repond, Grégoire Wang, Yue Gomes, Suzana Krishnakumar, Raga Siddarth, Prabha Swartz, Melody A. Hubbell, Jeffrey A. Briquez, Priscilla S. Membrane-localized neoantigens predict the efficacy of cancer immunotherapy |
title | Membrane-localized neoantigens predict the efficacy of cancer immunotherapy |
title_full | Membrane-localized neoantigens predict the efficacy of cancer immunotherapy |
title_fullStr | Membrane-localized neoantigens predict the efficacy of cancer immunotherapy |
title_full_unstemmed | Membrane-localized neoantigens predict the efficacy of cancer immunotherapy |
title_short | Membrane-localized neoantigens predict the efficacy of cancer immunotherapy |
title_sort | membrane-localized neoantigens predict the efficacy of cancer immunotherapy |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10439248/ https://www.ncbi.nlm.nih.gov/pubmed/37552990 http://dx.doi.org/10.1016/j.xcrm.2023.101145 |
work_keys_str_mv | AT goldbergerzoe membranelocalizedneoantigenspredicttheefficacyofcancerimmunotherapy AT hauertsylvie membranelocalizedneoantigenspredicttheefficacyofcancerimmunotherapy AT changkevin membranelocalizedneoantigenspredicttheefficacyofcancerimmunotherapy AT kurtanichtrevin membranelocalizedneoantigenspredicttheefficacyofcancerimmunotherapy AT alparaaront membranelocalizedneoantigenspredicttheefficacyofcancerimmunotherapy AT repondgregoire membranelocalizedneoantigenspredicttheefficacyofcancerimmunotherapy AT wangyue membranelocalizedneoantigenspredicttheefficacyofcancerimmunotherapy AT gomessuzana membranelocalizedneoantigenspredicttheefficacyofcancerimmunotherapy AT krishnakumarraga membranelocalizedneoantigenspredicttheefficacyofcancerimmunotherapy AT siddarthprabha membranelocalizedneoantigenspredicttheefficacyofcancerimmunotherapy AT swartzmelodya membranelocalizedneoantigenspredicttheefficacyofcancerimmunotherapy AT hubbelljeffreya membranelocalizedneoantigenspredicttheefficacyofcancerimmunotherapy AT briquezpriscillas membranelocalizedneoantigenspredicttheefficacyofcancerimmunotherapy |