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Published on: April 15, 2016
Lenvatinib recruits cytotoxic GZMK+CD8 T cells in hepatocellular carcinoma
Tomoharu Yamada1, Naoto Fujiwara2, Naoto Kubota3
1Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Background:
Lenvatinib was expected to enhance the effect of immune checkpoint inhibitors (ICIs) for unresectable HCC; however, their combination therapy failed to show the synergy in the phase III clinical trial.
Methods:
To elucidate lenvatinib-induced molecular modulation, we performed bulk RNA-sequencing and digital spatial profiling of 5 surgically resected human HCC specimens after lenvatinib treatment and 10 matched controls without any preceding therapy.
Findings:
Besides its direct antitumor effects, lenvatinib recruited cytotoxic GZMK+CD8 T cells in intratumor stroma by CXCL9 from tumor-associated macrophages, suggesting that lenvatinib-treated HCC is in the so-called excluded condition that can diminish ICI efficacy.
