Expression of leukocyte immunoglobulin-like receptor subfamily B expression on immune cells in hepatocellular carcinoma

Abstract

Background: Leukocyte immunoglobulin-like receptor subfamily B (LILRB) is a group of inhibitory receptors involved in innate immune mainly expressed on lymphoid and myelomonocytic cells. LILRB is proposed to serve as immune checkpoint like PD-1 and CTLA-4 for tumor treatment. We recently reported that the expression of LILRB2 in CD1c⁺ mDC from tumor tissue might suppress immune for HCC patients. However, the expression of all the LILRB family on other immune cells in peripheral blood and tumor microenvironment of HCC patients has not been systematically studied.

Methods: The expression of LILRB family (LILRB1, LILRB2, LILRB3, LILRB4 and LILRB5) on immune cells, including granulocytes, NK cells, NKT cells, monocyte subsets, TAMs, B cells, γδ T cells, CD4⁺ T cells, CD8⁺ T cells and MDSC subsets, was analyzed by flow cytometry in the peripheral blood of 20 HCC patients and 20 healthy donors as well as in the tumor and tumor free tissues of 10 HCC patients.

Results: LILRB1, LILRB2 and LILRB3 in granulocytes from peripheral blood were expressed increased in HCC patients compared with healthy donors. The expression of LILRB5 in NK cells and NKT cells from HCC blood were higher compared with healthy donors` blood. CD14⁺CD16⁺ monocyte subsets in blood of HCC patients expressed increased LILRB1 and LILRB4 than that in healthy donors. CD14⁺CD16^- monocyte subsets in blood of HCC patients expressed increased LILRB3 than that in healthy donors. Compared to corresponding TFL, LILRB3, LILRB4 and LILRB5 were expressed enhanced in TAMs from HCC tumors. LILRB1 expressed on the B cells both in the blood and tumor had significantly increased compared with healthy donors or corresponding TFL. Different from peripheral blood, in the HCC microenvironment, CD4⁺ T cells expressed lower LILRB2, LILRB3 and LILRB4 than that from TFL and CD8⁺ T cells expressed decreased LILRB2. And γδ T cells expressed LILRB1 in HCC blood and microenvironment. Surprisingly, the percentage of LILRB1 expressed on MDSC from HCC peripheral blood and tumors was lower than that from healthy donors and corresponding TFL.

Conclusions: This is the first systemically examination of the LILRB family expression on a variety of immune cells from both peripheral blood and microenvironment in HCC patients. The specific increasing expression of LILRB on immune cells may regulate innate and adaptive immune and impact on HCC progression. Our findings justify further investigation of LILRB function in HCC.

Keywords: HCC; LILRB family members; Tumor infiltrating lymphocytes; Tumor microenvironment.