Oncolytic herpes simplex virus propagates tertiary lymphoid structure formation via CXCL10/CXCR3 to boost antitumor immunity.

IF 5.9 1区生物学 Q2 CELL BIOLOGY

Cell Proliferation Pub Date : 2024-09-01 DOI:10.1111/cpr.13740

Meng-Jie Zhang, Wen-Ping Lin, Qing Wang, Shuo Wang, An Song, Yuan-Yuan Wang, Hao Li, Zhi-Jun Sun

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Abstract

Inducing tertiary lymphoid structure (TLS) formation can fuel antitumor immunity. It is necessary to create mouse models containing TLS to explore strategies of TLS formation. Oncolytic herpes simplex virus-1 (oHSV) exhibited intense effects in preclinical and clinical trials. However, the role of oHSV in TLS formation remains to be elucidated. Here, we observed the presence of TLS in 4MOSC1 and MC38 subcutaneous tumour models. Interestingly, oHSV evoked TLS formation, and increased infiltration of B cells and stem-like TCF1⁺CD8⁺ T cells proliferation. Mechanistically, oHSV increased the expression of TLS-related chemokines, along with upregulated CXCL10/CXCR3 to facilitate TLS formation. Notably, CXCL10 and CXCR3 were favourable prognostic factors for cancer patients, and closely related with immune cells infiltration. Inhibiting CXCL10/CXCR3 reduced TCF1⁺CD8⁺ T cells and granzyme B expression, and impaired oHSV-mediated TLS formation. Furthermore, oHSV-mediated TLS formation revealed superior response and survival rate when combined with αPD-1 treatment. Collectively, these findings indicate that oHSV recruits stem-like TCF1⁺CD8⁺ T cells through CXCL10/CXCR3 pathway to propagate TLS formation, and warrants future antitumor immunity development.

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肿瘤溶解性单纯疱疹病毒通过 CXCL10/CXCR3 促进三级淋巴结构的形成，从而增强抗肿瘤免疫力。

诱导三级淋巴结构（TLS）的形成可以增强抗肿瘤免疫力。有必要创建含有三级淋巴结构的小鼠模型，以探索三级淋巴结构的形成策略。肿瘤溶解性单纯疱疹病毒-1（oHSV）在临床前和临床试验中表现出强烈的效果。然而，oHSV 在 TLS 形成中的作用仍有待阐明。在这里，我们观察到 4MOSC1 和 MC38 皮下肿瘤模型中存在 TLS。有趣的是，oHSV诱发了TLS的形成，并增加了B细胞的浸润和干样TCF1+CD8+ T细胞的增殖。从机理上讲，oHSV 增加了 TLS 相关趋化因子的表达，并上调了 CXCL10/CXCR3 以促进 TLS 的形成。值得注意的是，CXCL10 和 CXCR3 是癌症患者的有利预后因素，与免疫细胞浸润密切相关。抑制 CXCL10/CXCR3 可减少 TCF1+CD8+ T 细胞和颗粒酶 B 的表达，并阻碍 oHSV 介导的 TLS 形成。此外，oHSV介导的TLS形成与αPD-1治疗相结合时，反应和存活率都更高。总之，这些研究结果表明，oHSV通过CXCL10/CXCR3途径招募干样TCF1+CD8+ T细胞，促进TLS的形成，值得在未来开发抗肿瘤免疫。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cell Proliferation 生物-细胞生物学

CiteScore

14.80

自引率

2.40%

发文量

198

审稿时长

1 months

期刊介绍： Cell Proliferation Focus: Devoted to studies into all aspects of cell proliferation and differentiation. Covers normal and abnormal states. Explores control systems and mechanisms at various levels: inter- and intracellular, molecular, and genetic. Investigates modification by and interactions with chemical and physical agents. Includes mathematical modeling and the development of new techniques. Publication Content: Original research papers Invited review articles Book reviews Letters commenting on previously published papers and/or topics of general interest By organizing the information in this manner, readers can quickly grasp the scope, focus, and publication content of Cell Proliferation.