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瘤性简单疹病毒通过CXCL10/CXCR3传播三级淋巴体结构形成,以提高抗瘤免疫力

Meng-Jie Zhang¹, Wen-Ping Lin¹, Qing Wang¹

¹State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Frontier Science Center for Immunology and Metabolism, Taikang Center for Life and Medical Sciences, Wuhan University, Wuhan, China.

Cell proliferation

|September 2, 2024

概括

瘤性简单疹病毒-1 (oHSV) 通过通过CXCL10/CXCR3通路招募类似干细胞的CD8+T细胞来促进三级淋巴细胞结构 (TLS) 的形成. 这种oHSV诱导的TLS形成增强了抗瘤免疫力,并改善了对免疫治疗的反应.

科学领域:

免疫学免疫学免疫学
在瘤学瘤学.
病毒学病毒学

背景情况:

三级淋巴体结构 (TLS) 对于抗瘤免疫至关重要.
瘤性简单疹病毒-1 (oHSV) 在癌症治疗中表现有前途,但其在TLS形成中的作用尚不清楚.

研究的目的:

在瘤模型中调查oHSV在TLS形成中的作用.
阐明oHSV影响TLS和抗瘤免疫力的机制.

主要方法:

使用了4MOSC1和MC38皮下瘤小鼠模型.
给药的oHSV和分析的TLS形成,免疫细胞透 (B细胞,TCF1+CD8+T细胞) 和化学激素表达 (CXCL10/CXCR3).
研究了CXCL10/CXCR3抑制对T细胞和大酶B的表达的影响,并评估了与αPD-1的联合治疗.

主要成果:

oHSV诱导了TLS的形成,并增加了B细胞和干细胞TCF1+CD8+T细胞的透.
oHSV上调了TLS相关的化学基因,特别是CXCL10/CXCR3,促进了TLS.
CXCL10/CXCR3通路对于oHSV介导的TLS形成和T细胞增殖至关重要;抑制损害了这些效应.
结合oHSV介导的TLS形成与αPD-1治疗,改善了抗瘤反应和生存率.

结论:

oHSV通过CXCL10/CXCR3通路招募类似干细胞的TCF1+CD8+T细胞来促进TLS的形成.
由oHSV诱导的TLS形成增强了抗瘤免疫力,并具有组合疗法的潜力,特别是与αPD-1的组合疗法.
已确定CXCL10和CXCR3是oHSV驱动的抗瘤免疫反应的关键参与者,也是癌症患者的有利预后因素.

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