Ho Won Jin, Zhu Qingfeng, Durham Jennifer, Popovic Aleksandra, Xavier Stephanie, Leatherman James, Mohan Aditya, Mo Guanglan, Zhang Shu, Gross Nicole, Charmsaz Soren, Lin Dongxia, Quong Derek, Wilt Brad, Kamel Ihab R, Weiss Matthew, Philosophe Benjamin, Burkhart Richard, Burns William R, Shubert Chris, Ejaz Aslam, He Jin, Deshpande Atul, Danilova Ludmila, Stein-O'Brien Genevieve, Sugar Elizabeth A, Laheru Daniel A, Anders Robert A, Fertig Elana J, Jaffee Elizabeth M, Yarchoan Mark
Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Nat Cancer. 2021 Sep;2(9):891-903. doi: 10.1038/s43018-021-00234-4. Epub 2021 Jul 29.
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 (NCT03299946). Of 15 patients enrolled, 12 (80%) underwent successful margin negative resection, and 5/12 (42%) patients had major pathologic responses. In-depth biospecimen profiling demonstrated an enrichment in T effector cells, as well as tertiary lymphoid structures, CD138+ plasma cells, and a distinct spatial arrangement of B cells in responders as compared to non-responders, indicating an orchestrated B-cell contribution to antitumor immunity in HCC.
根治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进行手术切除，且大多数接受手术切除的HCC最终都会复发。直到最近，HCC的新辅助全身治疗一直受到缺乏有效全身治疗药物的限制。在此，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，包括不符合传统切除标准的患者（NCT03299946）。在入组的15例患者中，12例（80%）成功进行了切缘阴性切除，5/12例（42%）患者有主要病理反应。深入的生物标本分析表明，与无反应者相比，反应者的T效应细胞、三级淋巴结构、CD138+浆细胞以及B细胞的独特空间排列有所富集，这表明B细胞在HCC的抗肿瘤免疫中发挥了协同作用。
