Cargando…
Salvage therapy expands highly cytotoxic and metabolically fit resilient CD8(+) T cells via ME1 up-regulation
Patients with advanced cancers who either do not experience initial response to or progress while on immune checkpoint inhibitors (ICIs) receive salvage radiotherapy to reduce tumor burden and tumor-related symptoms. Occasionally, some patients experience substantial global tumor regression with a r...
Autores principales: | , , , , , , , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Association for the Advancement of Science
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10651128/ https://www.ncbi.nlm.nih.gov/pubmed/37967193 http://dx.doi.org/10.1126/sciadv.adi2414 |
_version_ | 1785147597779894272 |
---|---|
author | Gicobi, Joanina K. Mao, Zhiming DeFranco, Grace Hirdler, Jacob B. Li, Ying Vianzon, Vianca V. Dellacecca, Emilia R. Hsu, Michelle A. Barham, Whitney Yan, Yiyi Mansfield, Aaron S. Lin, Yi Wu, Xiaosheng Hitosugi, Taro Owen, Dawn Grams, Michael P. Orme, Jacob J. Lucien, Fabrice Zeng, Hu Park, Sean S. Dong, Haidong |
author_facet | Gicobi, Joanina K. Mao, Zhiming DeFranco, Grace Hirdler, Jacob B. Li, Ying Vianzon, Vianca V. Dellacecca, Emilia R. Hsu, Michelle A. Barham, Whitney Yan, Yiyi Mansfield, Aaron S. Lin, Yi Wu, Xiaosheng Hitosugi, Taro Owen, Dawn Grams, Michael P. Orme, Jacob J. Lucien, Fabrice Zeng, Hu Park, Sean S. Dong, Haidong |
author_sort | Gicobi, Joanina K. |
collection | PubMed |
description | Patients with advanced cancers who either do not experience initial response to or progress while on immune checkpoint inhibitors (ICIs) receive salvage radiotherapy to reduce tumor burden and tumor-related symptoms. Occasionally, some patients experience substantial global tumor regression with a rebound of cytotoxic CD8(+) T cells. We have termed the rebound of cytotoxic CD8(+) T cells in response to salvage therapy as T cell resilience and examined the underlying mechanisms of resilience. Resilient T cells are enriched for CX3CR1(+) CD8(+) T cells with low mitochondrial membrane potential, accumulate less reactive oxygen species (ROS), and express more malic enzyme 1 (ME1). ME1 overexpression enhanced the cytotoxicity and expansion of effector CD8(+) T cells partially via the type I interferon pathway. ME1 also increased mitochondrial respiration while maintaining the redox state balance. ME1 increased the cytotoxicity of peripheral lymphocytes from patients with advanced cancers. Thus, preserved resilient T cells in patients rebound after salvage therapy and ME1 enhances their resiliency. |
format | Online Article Text |
id | pubmed-10651128 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | American Association for the Advancement of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-106511282023-11-15 Salvage therapy expands highly cytotoxic and metabolically fit resilient CD8(+) T cells via ME1 up-regulation Gicobi, Joanina K. Mao, Zhiming DeFranco, Grace Hirdler, Jacob B. Li, Ying Vianzon, Vianca V. Dellacecca, Emilia R. Hsu, Michelle A. Barham, Whitney Yan, Yiyi Mansfield, Aaron S. Lin, Yi Wu, Xiaosheng Hitosugi, Taro Owen, Dawn Grams, Michael P. Orme, Jacob J. Lucien, Fabrice Zeng, Hu Park, Sean S. Dong, Haidong Sci Adv Biomedicine and Life Sciences Patients with advanced cancers who either do not experience initial response to or progress while on immune checkpoint inhibitors (ICIs) receive salvage radiotherapy to reduce tumor burden and tumor-related symptoms. Occasionally, some patients experience substantial global tumor regression with a rebound of cytotoxic CD8(+) T cells. We have termed the rebound of cytotoxic CD8(+) T cells in response to salvage therapy as T cell resilience and examined the underlying mechanisms of resilience. Resilient T cells are enriched for CX3CR1(+) CD8(+) T cells with low mitochondrial membrane potential, accumulate less reactive oxygen species (ROS), and express more malic enzyme 1 (ME1). ME1 overexpression enhanced the cytotoxicity and expansion of effector CD8(+) T cells partially via the type I interferon pathway. ME1 also increased mitochondrial respiration while maintaining the redox state balance. ME1 increased the cytotoxicity of peripheral lymphocytes from patients with advanced cancers. Thus, preserved resilient T cells in patients rebound after salvage therapy and ME1 enhances their resiliency. American Association for the Advancement of Science 2023-11-15 /pmc/articles/PMC10651128/ /pubmed/37967193 http://dx.doi.org/10.1126/sciadv.adi2414 Text en Copyright © 2023 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). https://creativecommons.org/licenses/by-nc/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license (https://creativecommons.org/licenses/by-nc/4.0/) , which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited. |
spellingShingle | Biomedicine and Life Sciences Gicobi, Joanina K. Mao, Zhiming DeFranco, Grace Hirdler, Jacob B. Li, Ying Vianzon, Vianca V. Dellacecca, Emilia R. Hsu, Michelle A. Barham, Whitney Yan, Yiyi Mansfield, Aaron S. Lin, Yi Wu, Xiaosheng Hitosugi, Taro Owen, Dawn Grams, Michael P. Orme, Jacob J. Lucien, Fabrice Zeng, Hu Park, Sean S. Dong, Haidong Salvage therapy expands highly cytotoxic and metabolically fit resilient CD8(+) T cells via ME1 up-regulation |
title | Salvage therapy expands highly cytotoxic and metabolically fit resilient CD8(+) T cells via ME1 up-regulation |
title_full | Salvage therapy expands highly cytotoxic and metabolically fit resilient CD8(+) T cells via ME1 up-regulation |
title_fullStr | Salvage therapy expands highly cytotoxic and metabolically fit resilient CD8(+) T cells via ME1 up-regulation |
title_full_unstemmed | Salvage therapy expands highly cytotoxic and metabolically fit resilient CD8(+) T cells via ME1 up-regulation |
title_short | Salvage therapy expands highly cytotoxic and metabolically fit resilient CD8(+) T cells via ME1 up-regulation |
title_sort | salvage therapy expands highly cytotoxic and metabolically fit resilient cd8(+) t cells via me1 up-regulation |
topic | Biomedicine and Life Sciences |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10651128/ https://www.ncbi.nlm.nih.gov/pubmed/37967193 http://dx.doi.org/10.1126/sciadv.adi2414 |
work_keys_str_mv | AT gicobijoaninak salvagetherapyexpandshighlycytotoxicandmetabolicallyfitresilientcd8tcellsviame1upregulation AT maozhiming salvagetherapyexpandshighlycytotoxicandmetabolicallyfitresilientcd8tcellsviame1upregulation AT defrancograce salvagetherapyexpandshighlycytotoxicandmetabolicallyfitresilientcd8tcellsviame1upregulation AT hirdlerjacobb salvagetherapyexpandshighlycytotoxicandmetabolicallyfitresilientcd8tcellsviame1upregulation AT liying salvagetherapyexpandshighlycytotoxicandmetabolicallyfitresilientcd8tcellsviame1upregulation AT vianzonviancav salvagetherapyexpandshighlycytotoxicandmetabolicallyfitresilientcd8tcellsviame1upregulation AT dellaceccaemiliar salvagetherapyexpandshighlycytotoxicandmetabolicallyfitresilientcd8tcellsviame1upregulation AT hsumichellea salvagetherapyexpandshighlycytotoxicandmetabolicallyfitresilientcd8tcellsviame1upregulation AT barhamwhitney salvagetherapyexpandshighlycytotoxicandmetabolicallyfitresilientcd8tcellsviame1upregulation AT yanyiyi salvagetherapyexpandshighlycytotoxicandmetabolicallyfitresilientcd8tcellsviame1upregulation AT mansfieldaarons salvagetherapyexpandshighlycytotoxicandmetabolicallyfitresilientcd8tcellsviame1upregulation AT linyi salvagetherapyexpandshighlycytotoxicandmetabolicallyfitresilientcd8tcellsviame1upregulation AT wuxiaosheng salvagetherapyexpandshighlycytotoxicandmetabolicallyfitresilientcd8tcellsviame1upregulation AT hitosugitaro salvagetherapyexpandshighlycytotoxicandmetabolicallyfitresilientcd8tcellsviame1upregulation AT owendawn salvagetherapyexpandshighlycytotoxicandmetabolicallyfitresilientcd8tcellsviame1upregulation AT gramsmichaelp salvagetherapyexpandshighlycytotoxicandmetabolicallyfitresilientcd8tcellsviame1upregulation AT ormejacobj salvagetherapyexpandshighlycytotoxicandmetabolicallyfitresilientcd8tcellsviame1upregulation AT lucienfabrice salvagetherapyexpandshighlycytotoxicandmetabolicallyfitresilientcd8tcellsviame1upregulation AT zenghu salvagetherapyexpandshighlycytotoxicandmetabolicallyfitresilientcd8tcellsviame1upregulation AT parkseans salvagetherapyexpandshighlycytotoxicandmetabolicallyfitresilientcd8tcellsviame1upregulation AT donghaidong salvagetherapyexpandshighlycytotoxicandmetabolicallyfitresilientcd8tcellsviame1upregulation |