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Harnessing αβ T cell receptor mechanobiology to achieve the promise of immuno-oncology
T cell receptors (TCR) on cytolytic T lymphocytes (CTLs) recognize "foreign" antigens bound in the groove of major histocompatibility complex (MHC) molecules (H-2 in mouse and HLA in human) displayed on altered cells. These antigens are peptide fragments of proteins derived either from inf...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
National Academy of Sciences
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10318960/ https://www.ncbi.nlm.nih.gov/pubmed/37339184 http://dx.doi.org/10.1073/pnas.2215694120 |
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author | Reinherz, Ellis L. Hwang, Wonmuk Lang, Matthew J. |
author_facet | Reinherz, Ellis L. Hwang, Wonmuk Lang, Matthew J. |
author_sort | Reinherz, Ellis L. |
collection | PubMed |
description | T cell receptors (TCR) on cytolytic T lymphocytes (CTLs) recognize "foreign" antigens bound in the groove of major histocompatibility complex (MHC) molecules (H-2 in mouse and HLA in human) displayed on altered cells. These antigens are peptide fragments of proteins derived either from infectious pathogens or cellular transformations during cancer evolution. The conjoint ligand formed by the foreign peptide and MHC, termed pMHC, marks an aberrant cell as a target for CTL-mediated destruction. Recent data have provided compelling evidence that adaptive protection is achieved in a facile manner during immune surveillance when mechanical load consequent to cellular motion is applied to the bond formed between an αβ TCR and its pMHC ligand arrayed on a disease-altered cell. Mechanobiology maximizes both TCR specificity and sensitivity in comparison to receptor ligation in the absence of force. While the field of immunotherapy has made advances to impact the survival of cancer patients, the latest information relevant to T cell targeting and mechanotransduction has yet to be applied for T cell monitoring and treatment of patients in the clinic. Here we review these data, and challenge scientists and physicians to apply critical biophysical parameters of TCR mechanobiology to the medical oncology field, broadening treatment success within and among various cancer types. We assert that TCRs with digital ligand-sensing performance capability directed at sparsely as well as luminously displayed tumor-specific neoantigens and certain tumor-associated antigens can improve effective cancer vaccine development and immunotherapy paradigms. |
format | Online Article Text |
id | pubmed-10318960 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | National Academy of Sciences |
record_format | MEDLINE/PubMed |
spelling | pubmed-103189602023-07-05 Harnessing αβ T cell receptor mechanobiology to achieve the promise of immuno-oncology Reinherz, Ellis L. Hwang, Wonmuk Lang, Matthew J. Proc Natl Acad Sci U S A Perspective T cell receptors (TCR) on cytolytic T lymphocytes (CTLs) recognize "foreign" antigens bound in the groove of major histocompatibility complex (MHC) molecules (H-2 in mouse and HLA in human) displayed on altered cells. These antigens are peptide fragments of proteins derived either from infectious pathogens or cellular transformations during cancer evolution. The conjoint ligand formed by the foreign peptide and MHC, termed pMHC, marks an aberrant cell as a target for CTL-mediated destruction. Recent data have provided compelling evidence that adaptive protection is achieved in a facile manner during immune surveillance when mechanical load consequent to cellular motion is applied to the bond formed between an αβ TCR and its pMHC ligand arrayed on a disease-altered cell. Mechanobiology maximizes both TCR specificity and sensitivity in comparison to receptor ligation in the absence of force. While the field of immunotherapy has made advances to impact the survival of cancer patients, the latest information relevant to T cell targeting and mechanotransduction has yet to be applied for T cell monitoring and treatment of patients in the clinic. Here we review these data, and challenge scientists and physicians to apply critical biophysical parameters of TCR mechanobiology to the medical oncology field, broadening treatment success within and among various cancer types. We assert that TCRs with digital ligand-sensing performance capability directed at sparsely as well as luminously displayed tumor-specific neoantigens and certain tumor-associated antigens can improve effective cancer vaccine development and immunotherapy paradigms. National Academy of Sciences 2023-06-20 2023-07-04 /pmc/articles/PMC10318960/ /pubmed/37339184 http://dx.doi.org/10.1073/pnas.2215694120 Text en Copyright © 2023 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by-nc-nd/4.0/This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) . |
spellingShingle | Perspective Reinherz, Ellis L. Hwang, Wonmuk Lang, Matthew J. Harnessing αβ T cell receptor mechanobiology to achieve the promise of immuno-oncology |
title | Harnessing αβ T cell receptor mechanobiology to achieve the promise of immuno-oncology |
title_full | Harnessing αβ T cell receptor mechanobiology to achieve the promise of immuno-oncology |
title_fullStr | Harnessing αβ T cell receptor mechanobiology to achieve the promise of immuno-oncology |
title_full_unstemmed | Harnessing αβ T cell receptor mechanobiology to achieve the promise of immuno-oncology |
title_short | Harnessing αβ T cell receptor mechanobiology to achieve the promise of immuno-oncology |
title_sort | harnessing αβ t cell receptor mechanobiology to achieve the promise of immuno-oncology |
topic | Perspective |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10318960/ https://www.ncbi.nlm.nih.gov/pubmed/37339184 http://dx.doi.org/10.1073/pnas.2215694120 |
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