A potentially curative hepatic resection is the optimal treatment for hepatocellular carcinoma (HCC) but most patients are not candidates for resection and most resected HCCs eventually recur. Until recently, neoadjuvant systemic therapy for HCC has been limited by a lack of effective systemic agents. Here, in a single-arm phase 1b study, we evaluated the feasibility of neoadjuvant cabozantinib and nivolumab in patients with HCC, including patients outside of traditional resection criteria (ClinicalTrials.gov ID NCT03299946). Of 15 patients enrolled, 12 (80%) underwent successful margin-negative resection and 5 out of 12 (42%) had major pathological responses. In-depth biospecimen profiling demonstrated an enrichment in effector T cells, as well as tertiary lymphoid structures, CD138⁺ plasma cells, and a distinct spatial arrangement of B cells in responders compared to nonresponders, indicating an orchestrated B cell contribution to antitumor immunity in HCC.

潜在治愈性肝切除术是肝细胞癌 (HCC) 的最佳治疗方法，但大多数患者不适合切除，并且大多数切除的 HCC 最终会复发。直到最近，HCC 的新辅助全身治疗还因缺乏有效的全身药物而受到限制。在一项单臂 1b 期研究中，我们评估了新辅助卡博替尼和纳武单抗在 HCC 患者中的可行性，包括传统切除标准之外的患者 (ClinicalTrials.gov ID NCT03299946)。在纳入的 15 名患者中，12 名 (80%) 成功接受了切缘阴性切除，12 名患者中有 5 名 (42%) 出现重大病理反应。深入的生物样本分析表明，与无反应者相比，反应者中效应 T 细胞以及三级淋巴结构、CD138 ⁺浆细胞以及 B 细胞的独特空间排列富集，表明精心策划的 B 细胞对 HCC 抗肿瘤免疫的贡献。