Intratumoral administration is a widely used method for oncolytic virotherapy, as it enables immediate access of virus particles to the target tumor and potentially lead to the suppression of untreated distant tumors via in situ vaccination. However, because the injection volume and concentration of the virus solution are physically limited, the dose level cannot be increased. Additionally, efficacy in distant tumors needs improvement to prolong patient survival. Here, we demonstrate the benefit of oxaliplatin, with detailed mechanisms revealed through transcriptome analysis, which may provide a solution for the crucial deficiencies of oncolytic virotherapy. In virus-injected tumors, oxaliplatin improved virus retention through suppression of type I interferons. In distant virus-naive tumors, oxaliplatin induced alterations in the intratumoral macrophage characteristics, leading to the chemotaxis and recruitment of activated T cells and subsequently inducing an inflammatory state in the non-injected tumors. Our findings can be a trigger to change the therapeutic paradigm of oncolytic virotherapy for patients with systemic metastases.

中文翻译：

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与奥沙利铂联合使用通过重组瘤内巨噬细胞改善溶瘤病毒疗法的远隔效果


瘤内给药是一种广泛使用的溶瘤病毒疗法方法，因为它能够使病毒颗粒立即进入目标肿瘤，并有可能通过原位疫苗接种抑制未经治疗的远处肿瘤。但是，由于病毒溶液的注射量和浓度受到物理限制，因此不能增加剂量水平。此外，对远处肿瘤的疗效需要提高以延长患者生存期。在这里，我们展示了奥沙利铂的好处，并通过转录组分析揭示了详细的机制，这可能为溶瘤病毒疗法的关键缺陷提供解决方案。在病毒注射的肿瘤中，奥沙利铂通过抑制 I 型干扰素来改善病毒保留。在远处病毒初治肿瘤中，奥沙利铂诱导瘤内巨噬细胞特征的改变，导致活化 T 细胞的趋化性和募集，随后在未注射的肿瘤中诱导炎症状态。我们的研究结果可以触发改变全身性转移患者溶瘤病毒疗法的治疗范式。