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溶瘤腺病毒通过 STING 介导的 DC 激活促进血管正常化和非经典三级淋巴结构形成。

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

机构信息

Department of Infectious Diseases, the Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.

Department of Thoracic Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.

出版信息

Oncoimmunology. 2022 Jul 1;11(1):2093054. doi: 10.1080/2162402X.2022.2093054. eCollection 2022.

DOI:10.1080/2162402X.2022.2093054
PMID:35800155
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9255224/
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.

摘要

在肿瘤微环境（TME）中诱导完全的抗肿瘤免疫反应对于成功的癌症免疫治疗至关重要。在这里，我们报告说，携带 mIL-15 的溶瘤腺病毒（Ad-IL15）可以在癌症的小鼠模型中有效诱导抗肿瘤免疫反应并抑制肿瘤生长。我们发现，Ad-IL15 促进了 TME 中免疫细胞（包括树突状细胞（DCs）、T 细胞和自然杀伤（NK）细胞）的激活和浸润。出乎意料的是，我们观察到 Ad-IL15 还诱导了 TME 中的血管正常化和三级淋巴结构形成。此外，我们证明了 TME 中这些 Ad-IL15 诱导的变化取决于 DCs 中 Ad-IL15 诱导的 STING-TBK1-IRF3 途径的激活。总之，我们的研究结果表明，Ad-IL15 是一种癌症免疫治疗的候选药物，可促进 TME 中免疫细胞的激活和浸润、肿瘤血管正常化和三级淋巴结构形成。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a1d/9255224/90ba625b8c7e/KONI_A_2093054_F0008_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a1d/9255224/00df47237fd4/KONI_A_2093054_F0001_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a1d/9255224/f0955a32c747/KONI_A_2093054_F0002_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a1d/9255224/9bb42f9fcd51/KONI_A_2093054_F0003_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a1d/9255224/9d95d72734c2/KONI_A_2093054_F0004_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a1d/9255224/357d640b63e0/KONI_A_2093054_F0005_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a1d/9255224/ccb26fcb59c3/KONI_A_2093054_F0006_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a1d/9255224/865e77660f87/KONI_A_2093054_F0007_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a1d/9255224/90ba625b8c7e/KONI_A_2093054_F0008_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a1d/9255224/00df47237fd4/KONI_A_2093054_F0001_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a1d/9255224/f0955a32c747/KONI_A_2093054_F0002_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a1d/9255224/9bb42f9fcd51/KONI_A_2093054_F0003_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a1d/9255224/9d95d72734c2/KONI_A_2093054_F0004_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a1d/9255224/357d640b63e0/KONI_A_2093054_F0005_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a1d/9255224/ccb26fcb59c3/KONI_A_2093054_F0006_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a1d/9255224/865e77660f87/KONI_A_2093054_F0007_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a1d/9255224/90ba625b8c7e/KONI_A_2093054_F0008_OC.jpg

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