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Tumor-Targeted Gene Silencing IDO Synergizes PTT-Induced Apoptosis and Enhances Anti-tumor Immunity
Background: Photothermal therapy (PTT) has been demonstrated to be a promising cancer treatment approach because it can be modulated to induce apoptosis instead of necrosis via adjusting irradiation conditions. Recently, an abscopal anti-tumor immunity has been highlighted, in which PTT on the prima...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7295913/ https://www.ncbi.nlm.nih.gov/pubmed/32582152 http://dx.doi.org/10.3389/fimmu.2020.00968 |
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author | Zhang, Yujuan Feng, Yuanyuan Huang, Yanqing Wang, Yifan Qiu, Li Liu, Yanling Peng, Shanshan Li, Rong Kuang, Nanzhen Shi, Qiaofa Shi, Yanmei Chen, Yiguo Joshi, Rakesh Wang, Zhigang Yuan, Keng Min, Weiping |
author_facet | Zhang, Yujuan Feng, Yuanyuan Huang, Yanqing Wang, Yifan Qiu, Li Liu, Yanling Peng, Shanshan Li, Rong Kuang, Nanzhen Shi, Qiaofa Shi, Yanmei Chen, Yiguo Joshi, Rakesh Wang, Zhigang Yuan, Keng Min, Weiping |
author_sort | Zhang, Yujuan |
collection | PubMed |
description | Background: Photothermal therapy (PTT) has been demonstrated to be a promising cancer treatment approach because it can be modulated to induce apoptosis instead of necrosis via adjusting irradiation conditions. Recently, an abscopal anti-tumor immunity has been highlighted, in which PTT on the primary tumor also induced repression of distant tumors. In PTT cancer treatments, the mechanism and the role of immune checkpoints to enhance anti-tumor immunity needs to be investigated. Methods: We prepared a multi-functional gold nanorod reagent, GMPF-siIDO, that is composed of gold nanorods (GNRs) that act as the nano-platform and photothermal sensitizer; folic acid (FA) as the tumor-targeting moiety; and IDO-specific RNA (siIDO) as an immune-stimulator functionality for inducing anti-tumor immunity. For this study, we adjusted the irradiation condition of PTT to induce apoptosis and to silence the immune checkpoint indoleamine 2,3 dioxygeonase (IDO), simultaneously. Results: Our studies provide evidence that photothermal effects kill tumor cells mainly via inducing apoptosis, which can significantly improve antitumor immunity when IDO was down-regulated in TME through significant increases of localized CD8(+) and CD4(+) lymphocytes in tumor tissue, the downregulation of CD8(+) and CD4(+) lymphocyte apoptosis, and the upregulation of antitumor cytokines, TNF-α and IFN-γ. Conclusion: In this study, we, for the first time, validated the role of IDO as a negative regulator for both PTT-induced tumor cell apoptosis and anti-tumor immunity; IDO is a critical immune checkpoint that impedes PTT while combination of gene knockdown of IDO in TME enhances anti-tumor efficacy of PTT. |
format | Online Article Text |
id | pubmed-7295913 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-72959132020-06-23 Tumor-Targeted Gene Silencing IDO Synergizes PTT-Induced Apoptosis and Enhances Anti-tumor Immunity Zhang, Yujuan Feng, Yuanyuan Huang, Yanqing Wang, Yifan Qiu, Li Liu, Yanling Peng, Shanshan Li, Rong Kuang, Nanzhen Shi, Qiaofa Shi, Yanmei Chen, Yiguo Joshi, Rakesh Wang, Zhigang Yuan, Keng Min, Weiping Front Immunol Immunology Background: Photothermal therapy (PTT) has been demonstrated to be a promising cancer treatment approach because it can be modulated to induce apoptosis instead of necrosis via adjusting irradiation conditions. Recently, an abscopal anti-tumor immunity has been highlighted, in which PTT on the primary tumor also induced repression of distant tumors. In PTT cancer treatments, the mechanism and the role of immune checkpoints to enhance anti-tumor immunity needs to be investigated. Methods: We prepared a multi-functional gold nanorod reagent, GMPF-siIDO, that is composed of gold nanorods (GNRs) that act as the nano-platform and photothermal sensitizer; folic acid (FA) as the tumor-targeting moiety; and IDO-specific RNA (siIDO) as an immune-stimulator functionality for inducing anti-tumor immunity. For this study, we adjusted the irradiation condition of PTT to induce apoptosis and to silence the immune checkpoint indoleamine 2,3 dioxygeonase (IDO), simultaneously. Results: Our studies provide evidence that photothermal effects kill tumor cells mainly via inducing apoptosis, which can significantly improve antitumor immunity when IDO was down-regulated in TME through significant increases of localized CD8(+) and CD4(+) lymphocytes in tumor tissue, the downregulation of CD8(+) and CD4(+) lymphocyte apoptosis, and the upregulation of antitumor cytokines, TNF-α and IFN-γ. Conclusion: In this study, we, for the first time, validated the role of IDO as a negative regulator for both PTT-induced tumor cell apoptosis and anti-tumor immunity; IDO is a critical immune checkpoint that impedes PTT while combination of gene knockdown of IDO in TME enhances anti-tumor efficacy of PTT. Frontiers Media S.A. 2020-06-09 /pmc/articles/PMC7295913/ /pubmed/32582152 http://dx.doi.org/10.3389/fimmu.2020.00968 Text en Copyright © 2020 Zhang, Feng, Huang, Wang, Qiu, Liu, Peng, Li, Kuang, Shi, Shi, Chen, Joshi, Wang, Yuan and Min. http://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 | Immunology Zhang, Yujuan Feng, Yuanyuan Huang, Yanqing Wang, Yifan Qiu, Li Liu, Yanling Peng, Shanshan Li, Rong Kuang, Nanzhen Shi, Qiaofa Shi, Yanmei Chen, Yiguo Joshi, Rakesh Wang, Zhigang Yuan, Keng Min, Weiping Tumor-Targeted Gene Silencing IDO Synergizes PTT-Induced Apoptosis and Enhances Anti-tumor Immunity |
title | Tumor-Targeted Gene Silencing IDO Synergizes PTT-Induced Apoptosis and Enhances Anti-tumor Immunity |
title_full | Tumor-Targeted Gene Silencing IDO Synergizes PTT-Induced Apoptosis and Enhances Anti-tumor Immunity |
title_fullStr | Tumor-Targeted Gene Silencing IDO Synergizes PTT-Induced Apoptosis and Enhances Anti-tumor Immunity |
title_full_unstemmed | Tumor-Targeted Gene Silencing IDO Synergizes PTT-Induced Apoptosis and Enhances Anti-tumor Immunity |
title_short | Tumor-Targeted Gene Silencing IDO Synergizes PTT-Induced Apoptosis and Enhances Anti-tumor Immunity |
title_sort | tumor-targeted gene silencing ido synergizes ptt-induced apoptosis and enhances anti-tumor immunity |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7295913/ https://www.ncbi.nlm.nih.gov/pubmed/32582152 http://dx.doi.org/10.3389/fimmu.2020.00968 |
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