Downregulation of CD40 expression contributes to the accumulation of myeloid-derived suppressor cells in gastric tumors.

An elevated number of myeloid-derived suppressor cells (MDSCs) in tumor-bearing hosts has been recognized as a crucial mediator of tumor progression due to the cells potent ability to suppress antitumor immunity. Cluster of differentiation (CD) 40, as a suppressive phenotype expressed in MDSCs, is essential for MDSC-mediated immune suppression and the expansion of T regulatory cells. However, whether CD40 exerts a direct effect on the accumulation of MDSCs remains unclear. In the present study, CD40 was observed to be highly expressed on the MDSCs obtained from mice bearing gastric tumors. Notably, a significant decrease in the level of CD40 expression was observed in addition to an increased number of MDSCs during tumor progression. Further analysis revealed that the MDSC levels were found to positively correlate with tumor progression and that CD40 expression levels inversely correlate with the accumulation of MDSCs. To confirm the potent correlation between CD40 expression and the accumulation of MDSCs, the apoptosis of the MDSCs was detected using agonistic anti-CD40 treatment. The results indicated that CD40 activation induces apoptosis in MDSCs and that the downregulation of CD40 expression may contribute to MDSC accumulation by facilitating MDSC resistance to apoptosis. Thus, these observations provide a novel mechanism to improve our understanding of the involvement of CD40 in MDSC accumulation during cancer development.