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Oncolytic adenovirus promotes vascular normalization and nonclassical tertiary lymphoid structure formation through STING-mediated DC activation

Inducing a full antitumor immune response in the tumor microenvironment (TME) is essential for successful cancer immunotherapy. Here, we report that an oncolytic adenovirus carrying mIL-15 (Ad-IL15) can effectively induce antitumor immune response and inhibit tumor growth in a mouse model of cancer....

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Autores principales: He, Teng, Hao, Zhixing, Lin, Mingjie, Xin, Zhongwei, Chen, Yongyuan, Ouyang, Wei, Yang, Qi, Chen, Xiaoke, Zhou, Hui, Zhang, Wanying, Wu, Pin, Xu, Feng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9255224/
https://www.ncbi.nlm.nih.gov/pubmed/35800155
http://dx.doi.org/10.1080/2162402X.2022.2093054
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author He, Teng
Hao, Zhixing
Lin, Mingjie
Xin, Zhongwei
Chen, Yongyuan
Ouyang, Wei
Yang, Qi
Chen, Xiaoke
Zhou, Hui
Zhang, Wanying
Wu, Pin
Xu, Feng
author_facet He, Teng
Hao, Zhixing
Lin, Mingjie
Xin, Zhongwei
Chen, Yongyuan
Ouyang, Wei
Yang, Qi
Chen, Xiaoke
Zhou, Hui
Zhang, Wanying
Wu, Pin
Xu, Feng
author_sort He, Teng
collection PubMed
description Inducing a full antitumor immune response in the tumor microenvironment (TME) is essential for successful cancer immunotherapy. Here, we report that an oncolytic adenovirus carrying mIL-15 (Ad-IL15) can effectively induce antitumor immune response and inhibit tumor growth in a mouse model of cancer. We found that Ad-IL15 facilitated the activation and infiltration of immune cells, including dendritic cells (DCs), T cells and natural killer (NK) cells, in the TME. Unexpectedly, we observed that Ad-IL15 also induced vascular normalization and tertiary lymphoid structure formation in the TME. Moreover, we demonstrated these Ad-IL15-induced changes in the TME were depended on the Ad-IL15-induced activation of the STING-TBK1-IRF3 pathway in DCs. Taken together, our findings suggest that Ad-IL15 is a candidate for cancer immunotherapy that promotes immune cell activation and infiltration, tumor vascular normalization and tertiary lymphoid structure formation in the TME.
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spelling pubmed-92552242022-07-06 Oncolytic adenovirus promotes vascular normalization and nonclassical tertiary lymphoid structure formation through STING-mediated DC activation He, Teng Hao, Zhixing Lin, Mingjie Xin, Zhongwei Chen, Yongyuan Ouyang, Wei Yang, Qi Chen, Xiaoke Zhou, Hui Zhang, Wanying Wu, Pin Xu, Feng Oncoimmunology Original Research Inducing a full antitumor immune response in the tumor microenvironment (TME) is essential for successful cancer immunotherapy. Here, we report that an oncolytic adenovirus carrying mIL-15 (Ad-IL15) can effectively induce antitumor immune response and inhibit tumor growth in a mouse model of cancer. We found that Ad-IL15 facilitated the activation and infiltration of immune cells, including dendritic cells (DCs), T cells and natural killer (NK) cells, in the TME. Unexpectedly, we observed that Ad-IL15 also induced vascular normalization and tertiary lymphoid structure formation in the TME. Moreover, we demonstrated these Ad-IL15-induced changes in the TME were depended on the Ad-IL15-induced activation of the STING-TBK1-IRF3 pathway in DCs. Taken together, our findings suggest that Ad-IL15 is a candidate for cancer immunotherapy that promotes immune cell activation and infiltration, tumor vascular normalization and tertiary lymphoid structure formation in the TME. Taylor & Francis 2022-07-01 /pmc/articles/PMC9255224/ /pubmed/35800155 http://dx.doi.org/10.1080/2162402X.2022.2093054 Text en © 2022 The Author(s). Published with license by Taylor & Francis Group, LLC. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) ), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Research
He, Teng
Hao, Zhixing
Lin, Mingjie
Xin, Zhongwei
Chen, Yongyuan
Ouyang, Wei
Yang, Qi
Chen, Xiaoke
Zhou, Hui
Zhang, Wanying
Wu, Pin
Xu, Feng
Oncolytic adenovirus promotes vascular normalization and nonclassical tertiary lymphoid structure formation through STING-mediated DC activation
title Oncolytic adenovirus promotes vascular normalization and nonclassical tertiary lymphoid structure formation through STING-mediated DC activation
title_full Oncolytic adenovirus promotes vascular normalization and nonclassical tertiary lymphoid structure formation through STING-mediated DC activation
title_fullStr Oncolytic adenovirus promotes vascular normalization and nonclassical tertiary lymphoid structure formation through STING-mediated DC activation
title_full_unstemmed Oncolytic adenovirus promotes vascular normalization and nonclassical tertiary lymphoid structure formation through STING-mediated DC activation
title_short Oncolytic adenovirus promotes vascular normalization and nonclassical tertiary lymphoid structure formation through STING-mediated DC activation
title_sort oncolytic adenovirus promotes vascular normalization and nonclassical tertiary lymphoid structure formation through sting-mediated dc activation
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9255224/
https://www.ncbi.nlm.nih.gov/pubmed/35800155
http://dx.doi.org/10.1080/2162402X.2022.2093054
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