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TIGIT blockade enhances tumor response to radiotherapy via a CD103 + dendritic cell-dependent mechanism
Blockade of the T cell immunoreceptor with the immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT) can enhance innate and adaptive tumor immunity and radiotherapy (RT) can enhance anti-tumor immunity. However, our data suggest that TIGIT-mediated immune suppression may b...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer Berlin Heidelberg
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9813151/ https://www.ncbi.nlm.nih.gov/pubmed/35794399 http://dx.doi.org/10.1007/s00262-022-03227-z |
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author | Zhao, Kaikai Jiang, Liyang Si, Youjiao Zhou, Shujie Huang, Zhaoqin Meng, Xiangjiao |
author_facet | Zhao, Kaikai Jiang, Liyang Si, Youjiao Zhou, Shujie Huang, Zhaoqin Meng, Xiangjiao |
author_sort | Zhao, Kaikai |
collection | PubMed |
description | Blockade of the T cell immunoreceptor with the immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT) can enhance innate and adaptive tumor immunity and radiotherapy (RT) can enhance anti-tumor immunity. However, our data suggest that TIGIT-mediated immune suppression may be an impediment to such goals. Herein, we report on the synergistic effects of RT combined with anti-TIGIT therapy and the mechanism of their interaction. Treatment efficacy was assessed by measuring primary and secondary tumor growth, survival, and immune memory capacity. The function of CD103 + dendritic cells (DCs) under the combined treatment was assessed in wild-type and BATF3-deficient (BATF3(−/−)) mice. FMS-like tyrosine kinase 3 ligand (Flt3L) was used to confirm the role of CD103 + DCs in RT combined with anti-TIGIT therapy. TIGIT was upregulated in immune cells following RT in both esophageal squamous cell carcinoma patients and mouse models. Administration of the anti-TIGIT antibody enhanced the efficacy of RT through a CD8 + T cell-dependent mechanism. It was observed that RT and the anti-TIGIT antibody synergistically enhanced the accumulation of tumor-infiltrating DCs, which activated CD8 + T cells. The efficacy of the combination therapy was negated in the BATF3(−/−) mouse model. CD103 + DCs were required to promote the anti-tumor effects of combination therapy. Additionally, Flt3L therapy enhanced tumor response to RT combined with TIGIT blockade. Our study demonstrated TIGIT blockade can synergistically enhance anti-tumor T cell responses to RT via CD8 + T cells (dependent on CD103 + DCs), suggesting the clinical potential of targeting the TIGIT pathway and expanding CD103 + DCs in RT. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00262-022-03227-z. |
format | Online Article Text |
id | pubmed-9813151 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Springer Berlin Heidelberg |
record_format | MEDLINE/PubMed |
spelling | pubmed-98131512023-01-06 TIGIT blockade enhances tumor response to radiotherapy via a CD103 + dendritic cell-dependent mechanism Zhao, Kaikai Jiang, Liyang Si, Youjiao Zhou, Shujie Huang, Zhaoqin Meng, Xiangjiao Cancer Immunol Immunother Original Article Blockade of the T cell immunoreceptor with the immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT) can enhance innate and adaptive tumor immunity and radiotherapy (RT) can enhance anti-tumor immunity. However, our data suggest that TIGIT-mediated immune suppression may be an impediment to such goals. Herein, we report on the synergistic effects of RT combined with anti-TIGIT therapy and the mechanism of their interaction. Treatment efficacy was assessed by measuring primary and secondary tumor growth, survival, and immune memory capacity. The function of CD103 + dendritic cells (DCs) under the combined treatment was assessed in wild-type and BATF3-deficient (BATF3(−/−)) mice. FMS-like tyrosine kinase 3 ligand (Flt3L) was used to confirm the role of CD103 + DCs in RT combined with anti-TIGIT therapy. TIGIT was upregulated in immune cells following RT in both esophageal squamous cell carcinoma patients and mouse models. Administration of the anti-TIGIT antibody enhanced the efficacy of RT through a CD8 + T cell-dependent mechanism. It was observed that RT and the anti-TIGIT antibody synergistically enhanced the accumulation of tumor-infiltrating DCs, which activated CD8 + T cells. The efficacy of the combination therapy was negated in the BATF3(−/−) mouse model. CD103 + DCs were required to promote the anti-tumor effects of combination therapy. Additionally, Flt3L therapy enhanced tumor response to RT combined with TIGIT blockade. Our study demonstrated TIGIT blockade can synergistically enhance anti-tumor T cell responses to RT via CD8 + T cells (dependent on CD103 + DCs), suggesting the clinical potential of targeting the TIGIT pathway and expanding CD103 + DCs in RT. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00262-022-03227-z. Springer Berlin Heidelberg 2022-07-06 2023 /pmc/articles/PMC9813151/ /pubmed/35794399 http://dx.doi.org/10.1007/s00262-022-03227-z Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Original Article Zhao, Kaikai Jiang, Liyang Si, Youjiao Zhou, Shujie Huang, Zhaoqin Meng, Xiangjiao TIGIT blockade enhances tumor response to radiotherapy via a CD103 + dendritic cell-dependent mechanism |
title | TIGIT blockade enhances tumor response to radiotherapy via a CD103 + dendritic cell-dependent mechanism |
title_full | TIGIT blockade enhances tumor response to radiotherapy via a CD103 + dendritic cell-dependent mechanism |
title_fullStr | TIGIT blockade enhances tumor response to radiotherapy via a CD103 + dendritic cell-dependent mechanism |
title_full_unstemmed | TIGIT blockade enhances tumor response to radiotherapy via a CD103 + dendritic cell-dependent mechanism |
title_short | TIGIT blockade enhances tumor response to radiotherapy via a CD103 + dendritic cell-dependent mechanism |
title_sort | tigit blockade enhances tumor response to radiotherapy via a cd103 + dendritic cell-dependent mechanism |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9813151/ https://www.ncbi.nlm.nih.gov/pubmed/35794399 http://dx.doi.org/10.1007/s00262-022-03227-z |
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