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CD8(+) T cells maintain killing of MHC-I-negative tumor cells through the NKG2D–NKG2DL axis

The accepted paradigm for both cellular and anti-tumor immunity relies upon tumor cell killing by CD8(+) T cells recognizing cognate antigens presented in the context of target cell major histocompatibility complex (MHC) class I (MHC-I) molecules. Likewise, a classically described mechanism of tumor...

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Autores principales: Lerner, Emily C., Woroniecka, Karolina I., D’Anniballe, Vincent M., Wilkinson, Daniel S., Mohan, Aditya A., Lorrey, Selena J., Waibl-Polania, Jessica, Wachsmuth, Lucas P., Miggelbrink, Alexandra M., Jackson, Joshua D., Cui, Xiuyu, Raj, Jude A., Tomaszewski, William H., Cook, Sarah L., Sampson, John H., Patel, Anoop P., Khasraw, Mustafa, Gunn, Michael D., Fecci, Peter E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group US 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10518253/
https://www.ncbi.nlm.nih.gov/pubmed/37537301
http://dx.doi.org/10.1038/s43018-023-00600-4
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author Lerner, Emily C.
Woroniecka, Karolina I.
D’Anniballe, Vincent M.
Wilkinson, Daniel S.
Mohan, Aditya A.
Lorrey, Selena J.
Waibl-Polania, Jessica
Wachsmuth, Lucas P.
Miggelbrink, Alexandra M.
Jackson, Joshua D.
Cui, Xiuyu
Raj, Jude A.
Tomaszewski, William H.
Cook, Sarah L.
Sampson, John H.
Patel, Anoop P.
Khasraw, Mustafa
Gunn, Michael D.
Fecci, Peter E.
author_facet Lerner, Emily C.
Woroniecka, Karolina I.
D’Anniballe, Vincent M.
Wilkinson, Daniel S.
Mohan, Aditya A.
Lorrey, Selena J.
Waibl-Polania, Jessica
Wachsmuth, Lucas P.
Miggelbrink, Alexandra M.
Jackson, Joshua D.
Cui, Xiuyu
Raj, Jude A.
Tomaszewski, William H.
Cook, Sarah L.
Sampson, John H.
Patel, Anoop P.
Khasraw, Mustafa
Gunn, Michael D.
Fecci, Peter E.
author_sort Lerner, Emily C.
collection PubMed
description The accepted paradigm for both cellular and anti-tumor immunity relies upon tumor cell killing by CD8(+) T cells recognizing cognate antigens presented in the context of target cell major histocompatibility complex (MHC) class I (MHC-I) molecules. Likewise, a classically described mechanism of tumor immune escape is tumor MHC-I downregulation. Here, we report that CD8(+) T cells maintain the capacity to kill tumor cells that are entirely devoid of MHC-I expression. This capacity proves to be dependent instead on interactions between T cell natural killer group 2D (NKG2D) and tumor NKG2D ligands (NKG2DLs), the latter of which are highly expressed on MHC-loss variants. Necessarily, tumor cell killing in these instances is antigen independent, although prior T cell antigen-specific activation is required and can be furnished by myeloid cells or even neighboring MHC-replete tumor cells. In this manner, adaptive priming can beget innate killing. These mechanisms are active in vivo in mice as well as in vitro in human tumor systems and are obviated by NKG2D knockout or blockade. These studies challenge the long-advanced notion that downregulation of MHC-I is a viable means of tumor immune escape and instead identify the NKG2D–NKG2DL axis as a therapeutic target for enhancing T cell-dependent anti-tumor immunity against MHC-loss variants.
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spelling pubmed-105182532023-09-26 CD8(+) T cells maintain killing of MHC-I-negative tumor cells through the NKG2D–NKG2DL axis Lerner, Emily C. Woroniecka, Karolina I. D’Anniballe, Vincent M. Wilkinson, Daniel S. Mohan, Aditya A. Lorrey, Selena J. Waibl-Polania, Jessica Wachsmuth, Lucas P. Miggelbrink, Alexandra M. Jackson, Joshua D. Cui, Xiuyu Raj, Jude A. Tomaszewski, William H. Cook, Sarah L. Sampson, John H. Patel, Anoop P. Khasraw, Mustafa Gunn, Michael D. Fecci, Peter E. Nat Cancer Article The accepted paradigm for both cellular and anti-tumor immunity relies upon tumor cell killing by CD8(+) T cells recognizing cognate antigens presented in the context of target cell major histocompatibility complex (MHC) class I (MHC-I) molecules. Likewise, a classically described mechanism of tumor immune escape is tumor MHC-I downregulation. Here, we report that CD8(+) T cells maintain the capacity to kill tumor cells that are entirely devoid of MHC-I expression. This capacity proves to be dependent instead on interactions between T cell natural killer group 2D (NKG2D) and tumor NKG2D ligands (NKG2DLs), the latter of which are highly expressed on MHC-loss variants. Necessarily, tumor cell killing in these instances is antigen independent, although prior T cell antigen-specific activation is required and can be furnished by myeloid cells or even neighboring MHC-replete tumor cells. In this manner, adaptive priming can beget innate killing. These mechanisms are active in vivo in mice as well as in vitro in human tumor systems and are obviated by NKG2D knockout or blockade. These studies challenge the long-advanced notion that downregulation of MHC-I is a viable means of tumor immune escape and instead identify the NKG2D–NKG2DL axis as a therapeutic target for enhancing T cell-dependent anti-tumor immunity against MHC-loss variants. Nature Publishing Group US 2023-08-03 2023 /pmc/articles/PMC10518253/ /pubmed/37537301 http://dx.doi.org/10.1038/s43018-023-00600-4 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Lerner, Emily C.
Woroniecka, Karolina I.
D’Anniballe, Vincent M.
Wilkinson, Daniel S.
Mohan, Aditya A.
Lorrey, Selena J.
Waibl-Polania, Jessica
Wachsmuth, Lucas P.
Miggelbrink, Alexandra M.
Jackson, Joshua D.
Cui, Xiuyu
Raj, Jude A.
Tomaszewski, William H.
Cook, Sarah L.
Sampson, John H.
Patel, Anoop P.
Khasraw, Mustafa
Gunn, Michael D.
Fecci, Peter E.
CD8(+) T cells maintain killing of MHC-I-negative tumor cells through the NKG2D–NKG2DL axis
title CD8(+) T cells maintain killing of MHC-I-negative tumor cells through the NKG2D–NKG2DL axis
title_full CD8(+) T cells maintain killing of MHC-I-negative tumor cells through the NKG2D–NKG2DL axis
title_fullStr CD8(+) T cells maintain killing of MHC-I-negative tumor cells through the NKG2D–NKG2DL axis
title_full_unstemmed CD8(+) T cells maintain killing of MHC-I-negative tumor cells through the NKG2D–NKG2DL axis
title_short CD8(+) T cells maintain killing of MHC-I-negative tumor cells through the NKG2D–NKG2DL axis
title_sort cd8(+) t cells maintain killing of mhc-i-negative tumor cells through the nkg2d–nkg2dl axis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10518253/
https://www.ncbi.nlm.nih.gov/pubmed/37537301
http://dx.doi.org/10.1038/s43018-023-00600-4
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