Neoadjuvant cabozantinib and nivolumab convert locally advanced hepatocellular carcinoma into resectable disease with enhanced antitumor immunity

被引：249

作者：

Ho, Won Jin ^{[1
]}

Zhu, Qingfeng ^{[2
]}

Durham, Jennifer ^{[1
]}

Popovic, Aleksandra ^{[1
]}

Xavier, Stephanie ^{[1
]}

Leatherman, James ^{[1
]}

Mohan, Aditya ^{[1
]}

Mo, Guanglan ^{[1
]}

Zhang, Shu ^{[1
]}

Gross, Nicole ^{[1
]}

Charmsaz, Soren ^{[1
]}

Lin, Dongxia ^{[3
]}

Quong, Derek ^{[3
]}

Wilt, Brad ^{[1
]}

Kamel, Ihab R. ^{[4
]}

Weiss, Matthew ^{[5
]}

Philosophe, Benjamin ^{[5
]}

Burkhart, Richard ^{[5
]}

Burns, William R. ^{[5
]}

Shubert, Chris ^{[5
]}

Ejaz, Aslam ^{[5
]}

He, Jin ^{[5
]}

Deshpande, Atul ^{[6
,7
]}

Danilova, Ludmila ^{[7
]}

Stein-O'Brien, Genevieve ^{[6
,7
]}

Sugar, Elizabeth A. ^{[1
]}

Laheru, Daniel A. ^{[1
]}

Anders, Robert A. ^{[2
]}

Fertig, Elana J. ^{[6
,7
,8
,9
]}

Jaffee, Elizabeth M. ^{[1
]}

Yarchoan, Mark ^{[1
]}

机构：

[1] Johns Hopkins Univ, Sch Med, Dept Oncol, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21205 USA

[2] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA

[3] Fluidigm Corp, San Francisco, CA USA

[4] Johns Hopkins Univ, Sch Med, Dept Radiol & Radiol Sci, Baltimore, MD USA

[5] Johns Hopkins Univ, Sch Med, Dept Surg, Baltimore, MD 21205 USA

[6] Johns Hopkins Univ, McKusick Nathans Inst Genet Med, Sch Med, Baltimore, MD USA

[7] Johns Hopkins Univ, Sch Med, Div Biostat & Bioinformat, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA

[8] Johns Hopkins Univ, Sch Med, Dept Biomed Engn, Baltimore, MD 21205 USA

[9] Johns Hopkins Univ, Whiting Sch Engn, Dept Appl Math & Stat, Baltimore, MD USA

来源：

NATURE CANCER | 2021年 / 2卷 / 09期

基金：

美国国家卫生研究院;

关键词：

TRANSCATHETER ARTERIAL CHEMOEMBOLIZATION; B-CELLS; HEPATIC RESECTION; IN-VIVO; SURVIVAL; CANCER; IMMUNOTHERAPY; RECURRENCE; GROWTH; RECRUITMENT;

D O I：

10.1038/s43018-021-00234-4

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

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.

引用

页码：891 / +

页数：23

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