Successful human pregnancy requires the maternal immune system to recognize and tolerate the semi-allogeneic fetus. Myeloid-derived suppressor cells (MDSCs), which are capable of inhibiting T-cell responses, are highly increased in the early stages of pregnancy. Although recent reports indicate a role for MDSCs in fetal-maternal tolerance, little is known about the expansion of MDSCs during pregnancy. In the present study, we demonstrated that the trophoblast cell line HTR8/SVneo could instruct peripheral CD14 1 myelomonocytic cells toward a novel subpopulation of MDSCs, denoted as CD14 1 HLA-DR 2/low cells, with suppressive activity and increased expression of IDO1, ARG-1, and COX2. After interaction with HTR8/SVneo cells, CD14 1 myelomonocytic cells secrete high levels of CCL2, promoting the expression of signal transducer and activator of transcription 3. We utilized a neutralizing monoclonal antibody to reveal the prominent role of CCL2 in the induction of CD14 1 HLA-DR 2/low MDSCs. In combination, the results of the present study support a novel role for the cross-talk between the trophoblast cell line HTR8/SVneo and maternal CD14 1 myelomonocytic cells in initiating MDSCs induction, prompting a tolerogenic immune response to ensure a successful pregnancy. Cellular & Molecular Immunology

Crosstalk between tumor infiltrating macrophages and tumor cells is thought to play an indispensable role in oral squamous cell carcinomas (OSCC) by induction and maintenance of tolerance microenvironment. High infiltration of M2 macrophages and increasing expression of Kinesin family member 4A (Kif4A) in primary OSCC have been proved to correlate with greater tumoral size and poor clinical outcome. However, linkage between Kif4A and infiltrating macrophages in tumorigenesis and progression remains unclear. In the present study, we show that, the interaction between THP-1derived macrophage and OSCC cell line Cal-27 may up-regulate the Kif4A expression in both of them. Additionally, elevated soluble CCL2 in medium and more expression of CCR2 on macrophage were observed during the crosstalk. SiRNA of Kif4A and neutralizing antibody of CCL2 were utilized to identify that; increasing Kif4A can promote the recruitment of macrophages towards Cal-27 and educate them to M2 polarized macrophages via regulating CCL2/CCR2. In combination, the results of the present study may provide interesting clues to understanding the Kif4A-CCL2/CCR2-macrophage axis as a novel therapeutic target to improve the clinical outcome of OSCC.