Increased CD8+ T-cell Infiltration and Efficacy for Multikinase Inhibitors After PD-1 Blockade in Hepatocellular Carcinoma

Autor: Hiroto Kikuchi, Aya Matsui, Satoru Morita, Zohreh Amoozgar, Koetsu Inoue, Zhiping Ruan, Daniel Staiculescu, Jeffrey Sum-Lung Wong, Peigen Huang, Thomas Yau, Rakesh K Jain, Dan G Duda
Rok vydání: 2022
Předmět:
Zdroj: J Natl Cancer Inst
ISSN: 1460-2105
0027-8874
DOI: 10.1093/jnci/djac051
Popis: Immune checkpoint blockade combined with antiangiogenic therapy induces vascular normalization and antitumor immunity and is efficacious in hepatocellular carcinoma (HCC); but whether and how initial immunotherapy affects the efficacy of subsequent antiangiogenic therapy are unknown. We evaluated a cohort of HCC patients (n = 25) who received the pan–vascular endothelial growth factor receptor multikinase inhibitor sorafenib after initial therapy with an antiprogrammed cell death protein (PD)–1 antibody and found superior outcomes in these patients (12% overall response rate to sorafenib and a median overall survival of 12.1 months). To prove this potential benefit, we examined the impact of an anti–PD-1 antibody on response to subsequent sorafenib treatment in orthotopic models of murine HCC. Prior anti–PD-1 antibody treatment amplified HCC response to sorafenib therapy and increased survival (n = 8-9 mice per group, hazard ratio = 0.28, 95% confidence interval = 0.09 to 0.91; 2-sided P = .04). Anti–PD-1 therapy showed angioprotective effects on HCC vessels to subsequent sorafenib treatment, which enhanced the benefit of this therapy sequence in a CD8+ T-cell–dependent manner. This priming approach using immunotherapy provides an immediately translatable strategy for effective HCC treatment while reducing drug exposure.
Databáze: OpenAIRE
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