Recently, we showed that infection of primary lung tumor-bearing mice with oncolytic influenza A viruses (IAVs) led to strong virus-induced tumor cell lysis but also to restoration of immune competence of innate immune cells. Murine B16-F10 melanoma cells are known for their high lung tropism and progressive growth. As these cells are also highly permissive for IAVs, we analyzed their oncolytic and immunomodulatory efficiency against pulmonary B16-F10 lung metastases in vivo. IAV infection abrogated the melanoma-mediated immune suppression in the lung and induced a more than 50% cancer cell lysis. The oncolytic effect reached maximal efficacy 3 days post-infection, but it was not sustained over time. In order to maintain the virus-induced anti-tumor effect, mice with melanoma-derived lung cancers were treated in addition to influenza virus infection with an immune checkpoint inhibitor against programmed death-1 receptor (PD-1). The combined IAV and immune checkpoint inhibition (ICI) therapy resulted in a sustained anti-tumor efficacy, keeping the lung melanoma mass at day 12 of IAV infection still reduced by 50% over the control mice. In conclusion, ICI treatment strongly enhanced the oncolytic effect of influenza virus infection, suggesting that combined treatment is a promising approach against metastatic pulmonary melanoma.

最近，我们发现溶瘤性甲型流感病毒（IAV）感染了原发性肺肿瘤的小鼠，导致强力的病毒诱导的肿瘤细胞裂解，而且还恢复了先天免疫细胞的免疫能力。鼠B16-F10黑色素瘤细胞以其高肺向性和进行性生长而闻名。由于这些细胞对IAVs也是高度允许的，因此我们分析了它们在体内对肺B16-F10肺转移的溶瘤和免疫调节效率。IAV感染消除了黑色素瘤介导的肺部免疫抑制，并诱导了超过50％的癌细胞裂解。溶瘤作用在感染后3天达到最大功效，但随着时间的推移并没有持续。为了维持病毒诱导的抗肿瘤作用，除流感病毒感染外，还使用针对程序性死亡1受体（PD-1）的免疫检查点抑制剂治疗患有黑素瘤源性肺癌的小鼠。IAV和免疫检查点抑制（ICI）的联合治疗产生了持续的抗肿瘤功效，与对照组相比，IAV感染第12天时的肺部黑色素瘤肿块仍减少了50％。总之，ICI治疗可大大增强流感病毒感染的溶瘤作用，