Effect of CD16a, the surface receptor of Kupffer cells, on the growth of hepatocellular carcinoma cells

Abstract

FcγRIIIa (CD16) is a low-affinity Fc receptor of IgG. As the idio-binding receptor of IgG Fc, it plays an important role in the antibody-dependent cellular cytotoxicity of natural killer cells. The aim of the present study was to investigate the distribution of Kupffer cells (KCs) and the expression of their surface receptor FcγRIIIa in hepatocellular carcinoma. Furthermore, we also aimed to observe the functional mechanism of FcγRIIIa. Immunohistochemical analysis was employed to study KCs and FcγRIIIa. In order to explore the role of FcγRIIIa in the growth of cancer cells, KCs and H22 tumor cells were co-cultured in different serum. The mRNA expression levels of tumor necrosis factor (TNF)-α and FcγRIIIa were analyzed by RT-qPCR; the TNF-α and FcγRIIIa protein expression levels were examined by enzyme-linked immunosorbent assay and western blot analysis, respectively. Our results showed that the number of Kuppfer cells in cancerous tissues (21.6±7.8) was lower than those in para-cancerous (68.8±9.1) tissues and adjacent normal hepatic tissues (62.0±1.9) (P<0.01); this decreased with the reduction in the differentiation degree of cancer (P<0.05). FcγRIIIa-positive cells were similar in morphology to KCs, and their distributive tendency was coincident (P<0.05). The increase in CD16a mRNA levels in the group treated with immune serum was 3.9-, 4.9- and 3.9-fold greater than that in the ordinary serum group at different time points, and CD16a protein expression also markedly increased (P<0.05). However, these effects were inhibited by the addition of anti-IgG Fc serum (P<0.05). The results of the present study suggested that FcγRIIIa resided in KCs, and it contributed to the inhibition of the growth of liver tumor cells.

Immunometabolism: A novel perspective of liver cancer microenvironment and its influence on tumor progression

“…As guardians, macrophages are normally activated by inflammatory signals and together with CD4 + T cells eliminate precancerous senescent cells[ 19 ]. Kupffer cells directly show cytotoxicity against tumor cells[ 20 - 22 ]. In addition, macrophage-derived interleukin (IL)-12 hampers tumor progression by activating NK and NKT cells[ 23 , 24 ].…”

Multifunctional Antibodies Are Induced by the RTS,S Malaria Vaccine and Associated With Protection in a Phase 1/2a Trial

“…Interestingly, there was a more pronounced distinction between time to becoming malaria positive and high activity for binding to FcγRIII than FcγRIIa. This receptor may also be important as Kupffer cells, the resident liver macrophage, have also been shown to express FcγRIII in addition to FcγRIIa [46,47], and may clear opsonised sporozoites [48]. It is noteworthy that FcγRIII exists as two forms;…”

Clinical Data on Immunotherapy in Breast Cancer

“…The low-affinity CD16A-158F allele has been associated with a decreased clinical response to trastuzumab [99, 103]. CD16A is an Fc receptor expressed on the surfaces of natural killer cells and macrophages that plays roles in the signal transduction antibody-dependent immune response and phagocytosis [104, 105]. In a phase 1 study, Bang et al [105] first investigated the toxicity profile, optimal dosing schedule, pharmacokinetics, and antitumoral activity of single-agent therapy with margetuximab (0.1–6.0 mg/kg i.v.…”