Characterization of the Immune Microenvironment in Hepatocellular Carcinoma

Clin Cancer Res. 2017 Dec 1;23(23):7333-7339. doi: 10.1158/1078-0432.CCR-17-0950. Epub 2017 Sep 19.

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. Clin Cancer Res; 23(23); 7333-9. ©2017 AACR.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, CD / immunology
  • Antigens, CD / metabolism
  • Antigens, Differentiation, Myelomonocytic / immunology
  • Antigens, Differentiation, Myelomonocytic / metabolism
  • B7-H1 Antigen / immunology
  • B7-H1 Antigen / metabolism
  • Biomarkers, Tumor / immunology*
  • Biomarkers, Tumor / metabolism
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism
  • Carcinoma, Hepatocellular / immunology*
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / pathology
  • Female
  • Humans
  • Immunohistochemistry
  • Liver Neoplasms / immunology*
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology
  • Lymphocyte Activation Gene 3 Protein
  • Macrophages / immunology
  • Macrophages / metabolism
  • Male
  • Middle Aged
  • Programmed Cell Death 1 Receptor / immunology
  • Programmed Cell Death 1 Receptor / metabolism
  • Receptors, Cell Surface / immunology
  • Receptors, Cell Surface / metabolism
  • Survival Analysis
  • Tumor Microenvironment / immunology*
  • Young Adult

Substances

  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • B7-H1 Antigen
  • Biomarkers, Tumor
  • CD163 antigen
  • CD274 protein, human
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
  • Receptors, Cell Surface
  • Lymphocyte Activation Gene 3 Protein
  • Lag3 protein, human