"Homeostatic" Cytokines Enhance the Expression of PD-1, Tim-3, and Their Ligands on Myeloid Cells

We studied the expression of checkpoint molecules in monocyte subsets and monocytic myeloid-derived suppressor cells (M-MS) and the effect of homeostatic cytokines (IL-2, IL-7, IL-15) on the expression of PD-1/PD-L1 and Tim-3/Galectin-9 by myeloid cells. Monocytes and M-MS were shown to express PD-1 and Tim-3, and the proportions of PD-1⁺ monocytes and M-MS increased in multiple myeloma patients. Homeostatic cytokines enhanced the expression of inhibitory receptors (especially PD-1) by donor myeloid cells, the greatest effect was observed in M-MS. In addition, homeostatic cytokines increased PD-L1 expression in CD14⁺CD16^- monocytes and M-MS, and Galectin-9 in M-MS. Increased expression of checkpoint molecules by myeloid cells under the stimulation of IL-2, IL-7, and IL-15 is discussed as a feedback mechanism of T-cell homeostatic proliferation induced by lymphopenia.