作者
Won Jin Ho,Qingfeng Zhu,Jennifer N. Durham,Aleksandra Popović,Stephanie Xavier,James M. Leatherman,Aditya Mohan,Guanglan Mo,Shu Zhang,Nicole Groß,Soren Charmsaz,Derek Lin,Derek Quong,Brad Wilt,Ihab R. Kamel,Matthew J. Weiss,Benjamin Philosophe,Richard A. Burkhart,William R. Burns,Chris Shubert,Aslam Ejaz,Jin He,Atul Deshpande,Ludmila Danilova,Genevieve Stein-O’Brien,Elizabeth A. Sugar,Daniel A. Laheru,Robert A. Anders,Elana J. Fertig,Elizabeth M. Jaffee,Mark Yarchoan
摘要
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. Yarchoan and colleagues present a single-arm phase 1 clinical trial of cabozantinib with immune checkpoint inhibition for patients with hepatocellular carcinoma. Using high-dimensional spatial analysis, they identify immune features enriched in responders.