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

  • Oncoimmunology. 2022 Jul 1;11(1):2093054. doi: 10.1080/2162402X.2022.2093054.
Teng He  1 ,  Zhixing Hao  2  3 ,  Mingjie Lin  2  3 ,  Zhongwei Xin  2  3 ,  Yongyuan Chen  2  3 ,  Wei Ouyang  1 ,  Qi Yang  4 ,  Xiaoke Chen  2  3 ,  Hui Zhou  1 ,  Wanying Zhang  1 ,  Pin Wu  2  3 ,  Feng Xu  1
Affiliations
  • 1. Department of Infectious Diseases, the Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
  • 2. Department of Thoracic Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
  • 3. Key Laboratory of Tumor Microenvironment and Immune Therapy of Zhejiang Province, The Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
  • 4. Department of Emergency, the Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
PMID: 35800155 DOI: 10.1080/2162402X.2022.2093054
Abstract

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.

Keywords
DC; Oncolytic virus; STING; tertiary lymphoid structure; vascular normalization.
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