诱导三级淋巴结构（TLS）形成可以增强抗肿瘤免疫力。有必要建立含有TLS的小鼠模型来探索TLS的形成策略。溶瘤单纯疱疹病毒 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 TLS 形成，并增加 B 细胞的浸润和干细胞样 TCF1 CD8 T 细胞的增殖。从机制上讲，oHSV 增加了 TLS 相关趋化因子的表达，同时上调了 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，并且与免疫细胞浸润密切相关。抑制 CXCL10/CXCR3 会减少 TCF1 CD8 T 细胞和颗粒酶 B 的表达，并损害 oHSV 介导的 TLS 形成。此外，当与 αPD-1 治疗相结合时，oHSV 介导的 TLS 形成显示出优异的反应和存活率。总的来说，这些发现表明 oHSV 通过 CXCL10/CXCR3 途径招募干细胞样 TCF1 CD8 T 细胞来传播 TLS 形成，并保证未来抗肿瘤免疫的发展。© 2024 作者。北京干细胞与再生医学研究院和John Wiley联合出版的《细胞增殖》

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.© 2024 The Author(s). Cell Proliferation published by Beijing Institute for Stem Cell and Regenerative Medicine and John Wiley & Sons Ltd.