PD-1/TIM-3-Expressing Myeloid Cells During the Early Immune Reconstitution in Patients with Multiple Myeloma After High-Dose Chemotherapy.

Abstract

Background: In multiple myeloma (MM), immune checkpoint blockade is being explored as a treatment strategy. However, the role of inhibitory checkpoint receptors on myeloid cells remains poorly understood. The aim of our study was to investigate the expression of PD-1 and TIM-3 on monocytes and monocytic myeloid-derived suppressor cells (M-MDSCs) and their contribution to early immune reconstitution.

Methods: The count of monocytic cells and expression of PD-1 and TIM-3 was assessed by flow cytometry.

Results: At the engraftment, monocyte subsets counts were similar to pre-transplant values, while the relative content of M-MDSCs was significantly higher. The frequencies of TIM-3-positive cells among intermediate and non-classical monocytes were significantly increased. Incubation of mononuclear cells of MM patients in remission with homeostatic cytokines led to a significant increase in intermediate monocytes and a trend to an increase in the M-MDSCs count and stimulated the expression of PD-1 and TIM-3. PD-1 and TIM-3 expression on monocytes and M-MDSCs inversely correlated with lymphocyte count at the engraftment. TIM-3 expression on monocytic cells was associated with regulatory T-cell count. After auto-HSCT, PD-1/TIM-3-expressing cells exhibited significantly elevated IL-10 production (with decreased TNFα production).

Conclusion: PD-1 and TIM-3 on monocytic cells may play a significant role in immune reconstitution.