Here we report a phase 1b clinical trial testing the impact of oncolytic virotherapy with talimogene laherparepvec on cytotoxic T cell infiltration and therapeutic efficacy of the anti-PD-1 antibody pembrolizumab. Twenty-one patients with advanced melanoma were treated with talimogene laherparepvec followed by combination therapy with pembrolizumab. Therapy was generally well tolerated, with fatigue, fevers, and chills as the most common adverse events. No dose-limiting toxicities occurred. Confirmed objective response rate was 62%, with a complete response rate of 33% per immune-related response criteria. Patients who responded to combination therapy had increased CD8⁺ T cells, elevated PD-L1 protein expression, as well as IFN-γ gene expression on several cell subsets in tumors after talimogene laherparepvec treatment. Response to combination therapy did not appear to be associated with baseline CD8⁺ T cell infiltration or baseline IFN-γ signature. These findings suggest that oncolytic virotherapy may improve the efficacy of anti-PD-1 therapy by changing the tumor microenvironment. VIDEO ABSTRACT.

中文翻译：

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溶瘤病毒疗法促进肿瘤内T细胞浸润并改善抗PD-1免疫疗法。

在这里，我们报告了一项1b期临床试验，该试验测试了用talimogene laherparepvec进行溶瘤病毒疗法对细胞毒性T细胞浸润和抗PD-1抗体pembrolizumab的治疗功效的影响。21例晚期黑色素瘤患者接受了他莫替尼laherparepvec治疗，然后与派姆单抗联合治疗。一般而言，治疗耐受性良好，疲劳，发烧和发冷是最常见的不良事件。没有发生剂量限制性毒性。确认的客观应答率为62％，根据免疫相关应答标准，完全应答率为33％。对联合疗法有反应的患者的CD8 ⁺talimogene laherparepvec治疗后，肿瘤中多个细胞亚群的T细胞，PD-L1蛋白表达升高以及IFN-γ基因表达。对联合疗法的反应似乎与基线CD8 ⁺ T细胞浸润或基线IFN-γ信号无关。这些发现表明溶瘤病毒疗法可以通过改变肿瘤微环境来提高抗PD-1疗法的疗效。视频摘要。