Oncolytic adenovirus promotes vascular normalization and nonclassical tertiary lymphoid structure formation through STING-mediated DC activation.
Oncolytic adenovirus promotes vascular normalization and nonclassical tertiary lymphoid structure formation through STING-mediated DC activation.
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溶瘤腺病毒通过刺激性DC激活促进血管正常化和非经典三级淋巴结构的形成。
DOI：
10.1080/2162402x.2022.2093054
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发表时间：
2022
期刊：
影响因子：
7.2
通讯作者：
中科院分区：
文献类型：
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作者：
在肿瘤微环境（TME）中诱导全面的抗肿瘤免疫反应对于成功的癌症免疫治疗至关重要。在此，我们报道携带mIL-15（Ad-IL15）的溶瘤腺病毒可以有效诱导抗肿瘤免疫反应并抑制小鼠癌症模型中的肿瘤生长。我们发现 Ad-IL15 促进 TME 中免疫细胞的激活和浸润，包括树突状细胞 (DC)、T 细胞和自然杀伤 (NK) 细胞。出乎意料的是，我们观察到 Ad-IL15 还诱导 TME 中血管正常化和三级淋巴结构形成。此外，我们证明 Ad-IL15 诱导的 TME 变化取决于 Ad-IL15 诱导的 DC 中 STING-TBK1-IRF3 通路的激活。总而言之，我们的研究结果表明，Ad-IL15 是癌症免疫疗法的候选药物，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。
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.