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Improving the ex vivo expansion of human tumor-reactive CD8 + T cells by targeting toll-like receptors

Toll-like receptors (TLRs) are important pattern recognition receptor(s) known to mediate the sensing of invading pathogens and subsequent immune responses. In this study, we investigate whether TLRs could be explored for the preparation of human CD8(+) T cell products used in adoptive cell therapy...

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Autores principales: Qiu, Chenli, Wang, Jing, Zhu, Lingyan, Cheng, Xiaobo, Xia, Bili, Jin, Yanling, Qin, Ran, Zhang, LinXia, Hu, Huiliang, Yan, Jia, Zhao, Chen, Zhang, Xiaoyan, Xu, Jianqing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9659750/
https://www.ncbi.nlm.nih.gov/pubmed/36394017
http://dx.doi.org/10.3389/fbioe.2022.1027619
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author Qiu, Chenli
Wang, Jing
Zhu, Lingyan
Cheng, Xiaobo
Xia, Bili
Jin, Yanling
Qin, Ran
Zhang, LinXia
Hu, Huiliang
Yan, Jia
Zhao, Chen
Zhang, Xiaoyan
Xu, Jianqing
author_facet Qiu, Chenli
Wang, Jing
Zhu, Lingyan
Cheng, Xiaobo
Xia, Bili
Jin, Yanling
Qin, Ran
Zhang, LinXia
Hu, Huiliang
Yan, Jia
Zhao, Chen
Zhang, Xiaoyan
Xu, Jianqing
author_sort Qiu, Chenli
collection PubMed
description Toll-like receptors (TLRs) are important pattern recognition receptor(s) known to mediate the sensing of invading pathogens and subsequent immune responses. In this study, we investigate whether TLRs could be explored for the preparation of human CD8(+) T cell products used in adoptive cell therapy (ACT). Following characterization of TLRs expression on human CD8(+) T cells, we screened TLR-specific agonists for their ability to act in concert with anti-CD3 to stimulate the proliferation of these cells and corroborated the observed co-stimulatory effect by transcriptional profiling analyses. Consequently, we developed an optimal formulation for human CD8(+) T cell amplification by combining CD3/CD28 antibody, interleukin 7 (IL-7), interleukin 15 (IL-15), and three agonists respectively targeting TLR1/2, TLR2/6, and TLR5. This new formulation performed better in amplifying PD-1+CD8(+) T cells, a potential repertoire of tumor-reactive CD8(+) T cells, from tumor patients than the conventional formulation. Importantly, the expanded CD8(+) T cells showed restored functionality and consequently a robust anti-tumor activity in an in vitro co-culturing system. Together, our study established the utility of TLR agonists in ex vivo expansion of tumor-targeting CD8(+) T cells, thus providing a new avenue toward a more effective ACT.
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spelling pubmed-96597502022-11-15 Improving the ex vivo expansion of human tumor-reactive CD8 + T cells by targeting toll-like receptors Qiu, Chenli Wang, Jing Zhu, Lingyan Cheng, Xiaobo Xia, Bili Jin, Yanling Qin, Ran Zhang, LinXia Hu, Huiliang Yan, Jia Zhao, Chen Zhang, Xiaoyan Xu, Jianqing Front Bioeng Biotechnol Bioengineering and Biotechnology Toll-like receptors (TLRs) are important pattern recognition receptor(s) known to mediate the sensing of invading pathogens and subsequent immune responses. In this study, we investigate whether TLRs could be explored for the preparation of human CD8(+) T cell products used in adoptive cell therapy (ACT). Following characterization of TLRs expression on human CD8(+) T cells, we screened TLR-specific agonists for their ability to act in concert with anti-CD3 to stimulate the proliferation of these cells and corroborated the observed co-stimulatory effect by transcriptional profiling analyses. Consequently, we developed an optimal formulation for human CD8(+) T cell amplification by combining CD3/CD28 antibody, interleukin 7 (IL-7), interleukin 15 (IL-15), and three agonists respectively targeting TLR1/2, TLR2/6, and TLR5. This new formulation performed better in amplifying PD-1+CD8(+) T cells, a potential repertoire of tumor-reactive CD8(+) T cells, from tumor patients than the conventional formulation. Importantly, the expanded CD8(+) T cells showed restored functionality and consequently a robust anti-tumor activity in an in vitro co-culturing system. Together, our study established the utility of TLR agonists in ex vivo expansion of tumor-targeting CD8(+) T cells, thus providing a new avenue toward a more effective ACT. Frontiers Media S.A. 2022-10-31 /pmc/articles/PMC9659750/ /pubmed/36394017 http://dx.doi.org/10.3389/fbioe.2022.1027619 Text en Copyright © 2022 Qiu, Wang, Zhu, Cheng, Xia, Jin, Qin, Zhang, Hu, Yan, Zhao, Zhang and Xu. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Bioengineering and Biotechnology
Qiu, Chenli
Wang, Jing
Zhu, Lingyan
Cheng, Xiaobo
Xia, Bili
Jin, Yanling
Qin, Ran
Zhang, LinXia
Hu, Huiliang
Yan, Jia
Zhao, Chen
Zhang, Xiaoyan
Xu, Jianqing
Improving the ex vivo expansion of human tumor-reactive CD8 + T cells by targeting toll-like receptors
title Improving the ex vivo expansion of human tumor-reactive CD8 + T cells by targeting toll-like receptors
title_full Improving the ex vivo expansion of human tumor-reactive CD8 + T cells by targeting toll-like receptors
title_fullStr Improving the ex vivo expansion of human tumor-reactive CD8 + T cells by targeting toll-like receptors
title_full_unstemmed Improving the ex vivo expansion of human tumor-reactive CD8 + T cells by targeting toll-like receptors
title_short Improving the ex vivo expansion of human tumor-reactive CD8 + T cells by targeting toll-like receptors
title_sort improving the ex vivo expansion of human tumor-reactive cd8 + t cells by targeting toll-like receptors
topic Bioengineering and Biotechnology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9659750/
https://www.ncbi.nlm.nih.gov/pubmed/36394017
http://dx.doi.org/10.3389/fbioe.2022.1027619
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