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Autophagic flux restoration of senescent T cells improves antitumor activity of TCR‐engineered T cells
OBJECTIVES: Although adoptive cell therapy with T‐cell receptor‐engineered T cells (TCR‐Ts) has mediated effective antitumor responses in several cancers, senescence of T cells could impair the therapeutic effect of TCR‐Ts. Thus, it is essential to elucidate the characteristics of senescent TCR‐Ts a...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9512689/ https://www.ncbi.nlm.nih.gov/pubmed/36188121 http://dx.doi.org/10.1002/cti2.1419 |
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author | Zhang, Chaoting Sun, Yizhe Li, Shance Shen, Luyan Teng, Xia Xiao, Yefei Zhou, Ping Lu, Zheming |
author_facet | Zhang, Chaoting Sun, Yizhe Li, Shance Shen, Luyan Teng, Xia Xiao, Yefei Zhou, Ping Lu, Zheming |
author_sort | Zhang, Chaoting |
collection | PubMed |
description | OBJECTIVES: Although adoptive cell therapy with T‐cell receptor‐engineered T cells (TCR‐Ts) has mediated effective antitumor responses in several cancers, senescence of T cells could impair the therapeutic effect of TCR‐Ts. Thus, it is essential to elucidate the characteristics of senescent TCR‐Ts and how to subsequently improve their antitumor effect. Here, we focused on the influence of autophagy on TCR‐Ts, since autophagy is tightly associated with the regulation of T‐cell activation, proliferation and differentiation. METHODS: We first evaluated autophagy level of senescent TCR‐Ts, and then the senescent TCR‐Ts were expanded in vitro for 7 days with and without spermidine treatment, respectively. Furthermore, the proliferative potential, phenotypical characteristics and functionality of the propagated senescent TCR‐Ts were analysed in vitro and in vivo after 7‐day ex vivo expansion. RESULTS: We found that autophagic flux of senescent TCR‐T cells was significantly impaired. The restoration of autophagic flux via spermidine treatment reduced the expression of inhibitory immunoreceptors (PD‐1, TIM‐3 or LAG‐3), enhanced proliferation and effector functions and subsequently demonstrated the superior in vitro and in vivo antitumor activity of TCR‐Ts. CONCLUSION: These data suggest that spermidine treatment presents an opportunity to improve the antitumor effect of TCR‐Ts for the treatment of solid tumors. |
format | Online Article Text |
id | pubmed-9512689 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-95126892022-09-30 Autophagic flux restoration of senescent T cells improves antitumor activity of TCR‐engineered T cells Zhang, Chaoting Sun, Yizhe Li, Shance Shen, Luyan Teng, Xia Xiao, Yefei Zhou, Ping Lu, Zheming Clin Transl Immunology Short Communication OBJECTIVES: Although adoptive cell therapy with T‐cell receptor‐engineered T cells (TCR‐Ts) has mediated effective antitumor responses in several cancers, senescence of T cells could impair the therapeutic effect of TCR‐Ts. Thus, it is essential to elucidate the characteristics of senescent TCR‐Ts and how to subsequently improve their antitumor effect. Here, we focused on the influence of autophagy on TCR‐Ts, since autophagy is tightly associated with the regulation of T‐cell activation, proliferation and differentiation. METHODS: We first evaluated autophagy level of senescent TCR‐Ts, and then the senescent TCR‐Ts were expanded in vitro for 7 days with and without spermidine treatment, respectively. Furthermore, the proliferative potential, phenotypical characteristics and functionality of the propagated senescent TCR‐Ts were analysed in vitro and in vivo after 7‐day ex vivo expansion. RESULTS: We found that autophagic flux of senescent TCR‐T cells was significantly impaired. The restoration of autophagic flux via spermidine treatment reduced the expression of inhibitory immunoreceptors (PD‐1, TIM‐3 or LAG‐3), enhanced proliferation and effector functions and subsequently demonstrated the superior in vitro and in vivo antitumor activity of TCR‐Ts. CONCLUSION: These data suggest that spermidine treatment presents an opportunity to improve the antitumor effect of TCR‐Ts for the treatment of solid tumors. John Wiley and Sons Inc. 2022-09-26 /pmc/articles/PMC9512689/ /pubmed/36188121 http://dx.doi.org/10.1002/cti2.1419 Text en © 2022 The Authors. Clinical & Translational Immunology published by John Wiley & Sons Australia, Ltd on behalf of Australian and New Zealand Society for Immunology, Inc. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Short Communication Zhang, Chaoting Sun, Yizhe Li, Shance Shen, Luyan Teng, Xia Xiao, Yefei Zhou, Ping Lu, Zheming Autophagic flux restoration of senescent T cells improves antitumor activity of TCR‐engineered T cells |
title | Autophagic flux restoration of senescent T cells improves antitumor activity of TCR‐engineered T cells |
title_full | Autophagic flux restoration of senescent T cells improves antitumor activity of TCR‐engineered T cells |
title_fullStr | Autophagic flux restoration of senescent T cells improves antitumor activity of TCR‐engineered T cells |
title_full_unstemmed | Autophagic flux restoration of senescent T cells improves antitumor activity of TCR‐engineered T cells |
title_short | Autophagic flux restoration of senescent T cells improves antitumor activity of TCR‐engineered T cells |
title_sort | autophagic flux restoration of senescent t cells improves antitumor activity of tcr‐engineered t cells |
topic | Short Communication |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9512689/ https://www.ncbi.nlm.nih.gov/pubmed/36188121 http://dx.doi.org/10.1002/cti2.1419 |
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