Characterization of alpha-fetoprotein effects on dendritic cell and its function as effector immune response activator

Jeremiah Suryatenggara,1,2 Heri Wibowo,2 Wahyuni Lukita Atmodjo,3 George Mathew1,3 1Mochtar Riady Institute for Nanotechnology and Medical Science Group, Pelita Harapan University, Tangerang, 2Biomedical Science Graduate Programme, Faculty of Medicine, University of Indonesia, Jakarta, 3Faculty of Medicine, Pelita Harapan University, Tangerang, Indonesia Abstract: Tumor antigen alpha-fetoprotein (AFP) can promote immune tolerance toward tumor cells by inducing regulatory functions of the immune system. The purpose of this study was to characterize the effects of AFP on dendritic cells (DC) in their antitumor immune response stimulation and subsequent immune tolerance toward tumor cells. Monocytes were cultured in medium with GM-CSF and IL-4 and incubated for 6 days to generate immature DC (imDC). AFP was added into the treatment group at the beginning of the monocyte-derived DC culture. Mature DC (mDC) were generated by an addition of lipopolysaccharide (LPS) into the culture and incubation for another 48 hours. We observed that the addition of AFP in early DC culture was able to decrease the binding of LPS onto imDC surface, which lowered the strength of stimulation and consequently the maturity of DC. As expected, the expression of mDC surface markers, which are known to be crucial in effector cell proliferation and activation such as HLA-DR, CD40, CD80, CD83, and CD86, were confirmed to be reduced on AFP-exposed DC. DC potential in stimulating proliferation of CD4+ T cells was decreased, in line with the reduction of surface markers’ expression. Additionally, an increased secretion of cytokine TGF-β by DC was observed. In summary, AFP inhibited the effector immune responses while increasing the regulatory immune responses in DC. This might lead to tolerance toward antigens and tumor cell survival, such as in cases of hepatocellular carcinoma patients with high levels of AFP. Keywords: alpha-fetoprotein, dendritic cells, antigen-presenting cells, hepatocellular carcinoma, lipopolysaccharide, tumor immunoescape