Characterization of the immune microenvironment in hepatocellular carcinoma

Mark Yarchoan, Dongmei Xing, Lan Luan, Haiying Xu, Rajni B. Sharma, Aleksandra Popovic, Timothy M. Pawlik, Amy Kim, Qingfeng Zhu, Elizabeth Jaffee, Janis M Taube, Robert A Anders

Research output: Contribution to journalArticle

Abstract

Purpose: Hepatocellular carcinoma (HCC) often arises in the setting of chronic liver inflammation and may be responsive to novel immunotherapies. Experimental Design: To characterize the immune microenvironment in HCC, IHC staining was performed for CD8-positive T lymphocytes, PD-1–positive, and LAG-3–positive lymphocytes, CD163-positive macrophages, and PD-L1 expression in tumor and liver background from 29 cases of resected HCC. Results: Expression of CD8 was reduced in tumor, and expression of CD163 was reduced at the tumor interface. Positive clusters of PD-L1 expression were identified in 24 of 29 cases (83%), and positive expression of LAG-3 on tumor-infiltrating lymphocytes was identified in 19 of 29 cases (65%). The expression of both PD-L1 and LAG-3 was increased in tumor relative to liver background. No association between viral status or other clinicopathologic features and expression of any of the IHC markers investigated was noted. Conclusions: LAG-3 and PD-L1, two inhibitory molecules implicated in CD8 T-cell tolerance, are increased in most HCC tumors, providing a basis for investigating combinatorial checkpoint blockade with a LAG-3 and PD-L1 inhibitor in HCC.

Original languageEnglish (US)
Pages (from-to)7333-7339
Number of pages7
JournalClinical Cancer Research
Volume23
Issue number23
DOIs
StatePublished - Dec 1 2017

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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