Characterization of the Immune Microenvironment in Hepatocellular Carcinoma.

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.

• Authors: Mark Yarchoan, Dongmei Xing, Lan Luan, Haiying Xu, Rajni B Sharma, Aleksandra Popovic, Timothy M Pawlik, Amy K Kim, Qingfeng Zhu, Elizabeth M Jaffee, Janis M Taube, Robert A Anders
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 23 Issue 23 Pg. 7333-7339 (Dec 01 2017) ISSN: 1557-3265 [Electronic] United States
• PMID: 28928158 (Publication Type: Journal Article)
• Copyright: ©2017 American Association for Cancer Research.

Chemical References

• 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

Topics

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