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KMID : 1039320200200020128
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Journal of Liver Cancer
2020 Volume.20 No. 2 p.128 ~ p.134
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Infiltration of T Cells and Programmed Cell Death Ligand 1-expressing Macrophages as a Potential Predictor of Lenvatinib Response in Hepatocellular Carcinoma
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Sung Pil-Soo
Cho Sung-Woo
Lee Jae-Jun
Yang Hyun
Jang Jeong-Won
Bae Si-Hyun
Choi Jong-Young
Yoon Seung-Kew
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Abstract
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Background/Aims: Lenvatinib was recently proven to be non-inferior to sorafenib in treating unresectable hepatocellular carcinoma (HCC) in a phase-3 randomized controlled trial. In this study, we investigated whether the response to lenvatinib was affected by tumor immunogenicity.
Methods: Between May 2019 and April 2020, nine patients with intermediate-to-advanced HCC, who were treated with lenvatinib after liver biopsy, were enrolled. Immunohistochemical staining and multi-color flow cytometry were performed on specimens obtained from liver biopsy.
Results: Among the nine patients enrolled, four showed objective responses (complete responses+partial responses). Immunohistochemical staining for CD3, CD68, and programmed cell death ligand 1 (PD-L1) demonstrated that patients with objective responses showed marked infiltration of T cells and PD-L1-expressing macrophages in intra-tumoral and peri-tumoral tissues compared to those without objective responses. A significant difference in the numbers of infiltrated T cells, both in the intra-tumoral (P<0.01) and peri-tumoral regions (P<0.05), were identified between responders and non-responders. Regarding the number of infiltrated macrophages, no significant difference was found between the responders and non-responders, although the number of PD-L1-expressing tumor-associated macrophages was significantly higher in responders than that in non-responders (P<0.05).
Conclusions: Tumor immunogenicity, as indicated by T cell and PD-L1-positive macrophage infiltration, affects lenvatinib response in unresectable HCC.
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KEYWORD
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Hepatocellular carcinoma, Lenvatinib, PD-L1, Tumor-associated macrophage, Objective response
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