LIGHT/TNFSF14 promotes CAR-T cell trafficking and cytotoxicity through reversing immunosuppressive tumor microenvironment
Copyright © 2023 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved..
Tertiary lymphoid structures (TLSs) in tumor tissues facilitate immune cell trafficking and cytotoxicity, which benefits survival and favorable responses in immune therapy. Here, we observed a high correlation of tumor necrosis factor superfamily member 14 (LIGHT) expression with TLS signature genes, which are all markers for immune cell accumulation and better prognosis, through retrieving RNA sequencing (RNA-seq) data from patients with cancer, suggesting the potential of LIGHT in reconstituting a high immune-infiltrated tumor microenvironment. Accordingly, LIGHT co-expressed chimeric antigen receptor T (LIGHT CAR-T) cells not only showed enhanced cytotoxicity and cytokine production but also improved CCL19 and CCL21 expression by surrounding cells. And the supernatant of LIGHT CAR-T cells promoted T cell migration in a paracrine manner. Furthermore, LIGHT CAR-T cells showed superior anti-tumor efficacy and improved infiltration in comparison with conventional CAR-T cells in immunodeficient NSG mice. Accordingly, murine LIGHT-OT-1 T cells normalized tumor blood vessels and enforced intratumoral lymphoid structures in C57BL/6 syngeneic tumor mouse models, implying the potential of LIGHT CAR-T in clinical application. Taken together, our data revealed a straightforward strategy to optimize trafficking and cytotoxicity of CAR-T cells by redirecting TLSs through LIGHT expression, which has great potential to expand and optimize the application of CAR-T therapy in solid tumors.
Errataetall: |
CommentIn: Mol Ther. 2023 Sep 6;31(9):2570-2571. - PMID 37607540 |
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Medienart: |
E-Artikel |
Erscheinungsjahr: |
2023 |
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Erschienen: |
2023 |
Enthalten in: |
Zur Gesamtaufnahme - volume:31 |
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Enthalten in: |
Molecular therapy : the journal of the American Society of Gene Therapy - 31(2023), 9 vom: 06. Sept., Seite 2575-2590 |
Sprache: |
Englisch |
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Beteiligte Personen: |
Zhang, Na [VerfasserIn] |
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Links: |
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Themen: |
CAR-T |
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Anmerkungen: |
Date Completed 01.11.2023 Date Revised 01.11.2023 published: Print-Electronic CommentIn: Mol Ther. 2023 Sep 6;31(9):2570-2571. - PMID 37607540 Citation Status MEDLINE |
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doi: |
10.1016/j.ymthe.2023.06.015 |
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funding: |
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Förderinstitution / Projekttitel: |
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PPN (Katalog-ID): |
NLM35909452X |
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520 | |a Copyright © 2023 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved. | ||
520 | |a Tertiary lymphoid structures (TLSs) in tumor tissues facilitate immune cell trafficking and cytotoxicity, which benefits survival and favorable responses in immune therapy. Here, we observed a high correlation of tumor necrosis factor superfamily member 14 (LIGHT) expression with TLS signature genes, which are all markers for immune cell accumulation and better prognosis, through retrieving RNA sequencing (RNA-seq) data from patients with cancer, suggesting the potential of LIGHT in reconstituting a high immune-infiltrated tumor microenvironment. Accordingly, LIGHT co-expressed chimeric antigen receptor T (LIGHT CAR-T) cells not only showed enhanced cytotoxicity and cytokine production but also improved CCL19 and CCL21 expression by surrounding cells. And the supernatant of LIGHT CAR-T cells promoted T cell migration in a paracrine manner. Furthermore, LIGHT CAR-T cells showed superior anti-tumor efficacy and improved infiltration in comparison with conventional CAR-T cells in immunodeficient NSG mice. Accordingly, murine LIGHT-OT-1 T cells normalized tumor blood vessels and enforced intratumoral lymphoid structures in C57BL/6 syngeneic tumor mouse models, implying the potential of LIGHT CAR-T in clinical application. Taken together, our data revealed a straightforward strategy to optimize trafficking and cytotoxicity of CAR-T cells by redirecting TLSs through LIGHT expression, which has great potential to expand and optimize the application of CAR-T therapy in solid tumors | ||
650 | 4 | |a Journal Article | |
650 | 4 | |a Research Support, Non-U.S. Gov't | |
650 | 4 | |a CAR-T | |
650 | 4 | |a LIGHT/TNFSF14 | |
650 | 4 | |a TLSs | |
650 | 4 | |a prostate cancer | |
650 | 4 | |a tumor microenvironment | |
650 | 7 | |a Receptors, Chimeric Antigen |2 NLM | |
650 | 7 | |a Tumor Necrosis Factor Ligand Superfamily Member 14 |2 NLM | |
700 | 1 | |a Liu, Xiaohong |e verfasserin |4 aut | |
700 | 1 | |a Qin, Juliang |e verfasserin |4 aut | |
700 | 1 | |a Sun, Yue |e verfasserin |4 aut | |
700 | 1 | |a Xiong, Hao |e verfasserin |4 aut | |
700 | 1 | |a Lin, Boxu |e verfasserin |4 aut | |
700 | 1 | |a Liu, Kexin |e verfasserin |4 aut | |
700 | 1 | |a Tan, Binghe |e verfasserin |4 aut | |
700 | 1 | |a Zhang, Chenglin |e verfasserin |4 aut | |
700 | 1 | |a Huang, Chenshen |e verfasserin |4 aut | |
700 | 1 | |a Ren, Shancheng |e verfasserin |4 aut | |
700 | 1 | |a Liu, Mingyao |e verfasserin |4 aut | |
700 | 1 | |a Du, Bing |e verfasserin |4 aut | |
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