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

Teng He; Zhixing Hao; Mingjie Lin; Zhongwei Xin; Yongyuan Chen; Wei Ouyang; Qi Yang; Xiaoke Chen; Hui Zhou; Wanying Zhang; Pin Wu; Feng Xu

doi:10.1080/2162402X.2022.2093054

OncoImmunology (Dec 2022)

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

Teng He,
Zhixing Hao,
Mingjie Lin,
Zhongwei Xin,
Yongyuan Chen,
Wei Ouyang,
Qi Yang,
Xiaoke Chen,
Hui Zhou,
Wanying Zhang,
Pin Wu,
Feng Xu

Affiliations

Teng He: Department of Infectious Diseases, the Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
Zhixing Hao: Department of Thoracic Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
Mingjie Lin: Department of Thoracic Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
Zhongwei Xin: Department of Thoracic Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
Yongyuan Chen: Department of Thoracic Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
Wei Ouyang: Department of Infectious Diseases, the Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
Qi Yang: Department of Emergency, the Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
Xiaoke Chen: Department of Thoracic Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
Hui Zhou: Department of Infectious Diseases, the Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
Wanying Zhang: Department of Infectious Diseases, the Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
Pin Wu: Department of Thoracic Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China
Feng Xu: Department of Infectious Diseases, the Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China

DOI: https://doi.org/10.1080/2162402X.2022.2093054
Journal volume & issue: Vol. 11, no. 1

Abstract

Read online

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.

Published in OncoImmunology

ISSN: 2162-402X (Online)
Publisher: Taylor & Francis Group
Country of publisher: United Kingdom
LCC subjects: Medicine: Internal medicine: Specialties of internal medicine: Immunologic diseases. Allergy; Medicine: Internal medicine: Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Website: https://www.tandfonline.com/journals/koni

About the journal

Abstract

Keywords