Triple-negative breast cancer (TNBC) is an aggressive disease for which treatment options are limited and associated with severe toxicities. Immunotherapeutic approaches like immune checkpoint inhibitors (ICIs) are a potential strategy, but clinical trials have demonstrated limited success in this patient cohort. Clinical studies using ICIs have revealed that patients with preexisting anticancer immunity are the most responsive. Given that oncolytic viruses (OVs) induce antitumor immunity, we investigated their use as an ICI-sensitizing approach. Using a therapeutic model that mimics the course of treatment for women with newly diagnosed TNBC, we demonstrate that early OV treatment coupled with surgical resection provides long-term benefits. OV therapy sensitizes otherwise refractory TNBC to immune checkpoint blockade, preventing relapse in most of the treated animals. We suggest that OV therapy in combination with immune checkpoint blockade warrants testing as a neoadjuvant treatment option in the window of opportunity between TNBC diagnosis and surgical resection.

三阴性乳腺癌（TNBC）是一种侵袭性疾病，其治疗选择有限，并伴有严重的毒性。像免疫检查点抑制剂（ICIs）这样的免疫治疗方法是一种潜在的策略，但是临床试验证明该患者队列的成功有限。使用ICI的临床研究表明，已存在抗癌免疫力的患者反应最迅速。鉴于溶瘤病毒（OVs）诱导抗肿瘤免疫，我们研究了它们作为ICI敏化方法的用途。使用模拟新诊断为TNBC的妇女的治疗过程的治疗模型，我们证明了早期OV治疗与手术切除相结合可带来长期益处。OV治疗可使原本难治的TNBC对免疫检查点封锁敏感，防止大多数被治疗的动物复发。我们建议在TNBC诊断和手术切除之间的机会之窗中，将OV治疗与免疫检查点封锁相结合应作为新辅助治疗方法进行测试。