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Co-expression of a PD-L1-specific chimeric switch receptor augments the efficacy and persistence of CAR T cells via the CD70-CD27 axis
Co-expression of chimeric switch receptors (CSRs) specific for PD-L1 improves the antitumor effects of chimeric antigen receptor (CAR) T cells. However, the effects of trans-recognition between CSRs and PD-L1 expressed by activated CAR T cells remain unclear. Here, we design a CSR specific for PD-L1...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9561169/ https://www.ncbi.nlm.nih.gov/pubmed/36229619 http://dx.doi.org/10.1038/s41467-022-33793-w |
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author | Qin, Le Cui, Yuanbin Yuan, Tingjie Chen, Dongmei Zhao, Ruocong Li, Shanglin Jiang, Zhiwu Wu, Qiting Long, Youguo Wang, Suna Tang, Zhaoyang Pan, Huixia Li, Xiaoping Wei, Wei Yang, Jie Luo, Xuequn Zhang, Zhenfeng Tang, Qiannan Liu, Pentao Weinkove, Robert Yao, Yao Qin, Dajiang Thiery, Jean Paul Li, Peng |
author_facet | Qin, Le Cui, Yuanbin Yuan, Tingjie Chen, Dongmei Zhao, Ruocong Li, Shanglin Jiang, Zhiwu Wu, Qiting Long, Youguo Wang, Suna Tang, Zhaoyang Pan, Huixia Li, Xiaoping Wei, Wei Yang, Jie Luo, Xuequn Zhang, Zhenfeng Tang, Qiannan Liu, Pentao Weinkove, Robert Yao, Yao Qin, Dajiang Thiery, Jean Paul Li, Peng |
author_sort | Qin, Le |
collection | PubMed |
description | Co-expression of chimeric switch receptors (CSRs) specific for PD-L1 improves the antitumor effects of chimeric antigen receptor (CAR) T cells. However, the effects of trans-recognition between CSRs and PD-L1 expressed by activated CAR T cells remain unclear. Here, we design a CSR specific for PD-L1 (CARP), containing the transmembrane and cytoplasmic signaling domains of CD28 but not the CD3 ζ chain. We show that CARP T cells enhance the antitumor activity of anti-mesothelin CAR (CARMz) T cells in vitro and in vivo. In addition, confocal microscopy indicates that PD-L1 molecules on CARMz T cells accumulate at cell-cell contacts with CARP T cells. Using single-cell RNA-sequencing analysis, we reveal that CARP T cells promote CARMz T cells differentiation into central memory-like T cells, upregulate genes related to Th1 cells, and downregulate Th2-associated cytokines through the CD70-CD27 axis. Moreover, these effects are not restricted to PD-L1, as CAR19 T cells expressing anti-CD19 CSR exhibit similar effects on anti-PSCA CAR T cells with truncated CD19 expression. These findings suggest that target trans-recognition by CSRs on CAR T cells may improve the efficacy and persistence of CAR T cells via the CD70-CD27 axis. |
format | Online Article Text |
id | pubmed-9561169 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-95611692022-10-15 Co-expression of a PD-L1-specific chimeric switch receptor augments the efficacy and persistence of CAR T cells via the CD70-CD27 axis Qin, Le Cui, Yuanbin Yuan, Tingjie Chen, Dongmei Zhao, Ruocong Li, Shanglin Jiang, Zhiwu Wu, Qiting Long, Youguo Wang, Suna Tang, Zhaoyang Pan, Huixia Li, Xiaoping Wei, Wei Yang, Jie Luo, Xuequn Zhang, Zhenfeng Tang, Qiannan Liu, Pentao Weinkove, Robert Yao, Yao Qin, Dajiang Thiery, Jean Paul Li, Peng Nat Commun Article Co-expression of chimeric switch receptors (CSRs) specific for PD-L1 improves the antitumor effects of chimeric antigen receptor (CAR) T cells. However, the effects of trans-recognition between CSRs and PD-L1 expressed by activated CAR T cells remain unclear. Here, we design a CSR specific for PD-L1 (CARP), containing the transmembrane and cytoplasmic signaling domains of CD28 but not the CD3 ζ chain. We show that CARP T cells enhance the antitumor activity of anti-mesothelin CAR (CARMz) T cells in vitro and in vivo. In addition, confocal microscopy indicates that PD-L1 molecules on CARMz T cells accumulate at cell-cell contacts with CARP T cells. Using single-cell RNA-sequencing analysis, we reveal that CARP T cells promote CARMz T cells differentiation into central memory-like T cells, upregulate genes related to Th1 cells, and downregulate Th2-associated cytokines through the CD70-CD27 axis. Moreover, these effects are not restricted to PD-L1, as CAR19 T cells expressing anti-CD19 CSR exhibit similar effects on anti-PSCA CAR T cells with truncated CD19 expression. These findings suggest that target trans-recognition by CSRs on CAR T cells may improve the efficacy and persistence of CAR T cells via the CD70-CD27 axis. Nature Publishing Group UK 2022-10-13 /pmc/articles/PMC9561169/ /pubmed/36229619 http://dx.doi.org/10.1038/s41467-022-33793-w Text en © The Author(s) 2022 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 Qin, Le Cui, Yuanbin Yuan, Tingjie Chen, Dongmei Zhao, Ruocong Li, Shanglin Jiang, Zhiwu Wu, Qiting Long, Youguo Wang, Suna Tang, Zhaoyang Pan, Huixia Li, Xiaoping Wei, Wei Yang, Jie Luo, Xuequn Zhang, Zhenfeng Tang, Qiannan Liu, Pentao Weinkove, Robert Yao, Yao Qin, Dajiang Thiery, Jean Paul Li, Peng Co-expression of a PD-L1-specific chimeric switch receptor augments the efficacy and persistence of CAR T cells via the CD70-CD27 axis |
title | Co-expression of a PD-L1-specific chimeric switch receptor augments the efficacy and persistence of CAR T cells via the CD70-CD27 axis |
title_full | Co-expression of a PD-L1-specific chimeric switch receptor augments the efficacy and persistence of CAR T cells via the CD70-CD27 axis |
title_fullStr | Co-expression of a PD-L1-specific chimeric switch receptor augments the efficacy and persistence of CAR T cells via the CD70-CD27 axis |
title_full_unstemmed | Co-expression of a PD-L1-specific chimeric switch receptor augments the efficacy and persistence of CAR T cells via the CD70-CD27 axis |
title_short | Co-expression of a PD-L1-specific chimeric switch receptor augments the efficacy and persistence of CAR T cells via the CD70-CD27 axis |
title_sort | co-expression of a pd-l1-specific chimeric switch receptor augments the efficacy and persistence of car t cells via the cd70-cd27 axis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9561169/ https://www.ncbi.nlm.nih.gov/pubmed/36229619 http://dx.doi.org/10.1038/s41467-022-33793-w |
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