Expression of checkpoint molecules by regulatory T cells in multiple myeloma

In multiple myeloma (MM), the content of T lymphocytes expressing “checkpoint” molecules PD-1, TIM-3, LAG-3, etc. is increased. Regulatory T cells (Treg) can suppress antitumor immune response and play a sufficient role in MM pathogenesis. Like effector T lymphocytes, some Tregs express checkpoint receptors PD-1, TIM-3, etc., however, the biological meaning of such expression, as well as the consequences of blockade of these receptors, are not clear. The significance of type I regulatory T cells (Tr1), which produce the immunosuppressive cytokine interleukin-10, in MM also remains unexplored. The purpose of this work was to study the content of PD-1- and TIM-3-expressing Tregs and Tr1 in patients with MM. The study included 36 patients with MM and 24 matched healthy donors. The content of CD4 + CD25 hi CD127-FoxP3 + Tregs and IL-10-producing CD4 + IL-10 + Tr1 populations expressing PD-1 and TIM-3 was assessed in peripheral blood (PB) and bone marrow (BM) by flow cytometry. The relative content of circulating CD4 + CD25 hi CD127-FoxP3 + Tregs and IL-10-producing CD4 + IL-10 + Tr1 was significantly higher in MM patients compared to healthy donors. A higher relative content of IL-10-producing T lymphocytes was noted compared to Treg. The relative content of Tregs and Tr1 in BM samples did not differ significantly from PB values. The proportion of Tregs expressing PD-1 and TIM-3 in patients with MM did not differ significantly from the values in healthy donors. The content of PD-1- and TIM-3-positive CD4 + IL-10 + T cells was significantly higher in PB samples from MM patients compared to donors. IL-10-producing CD4 + T cells constitute a significant proportion of T lymphocytes in the PB and BM of patients with MM and may play an important role in the pathogenesis of MM. Their content exceeds that of CD4 + CD25 hi CD127-FoxP3 + Treg. A relatively small number of Tregs express the checkpoint receptors PD-1 and TIM-3, no different from donors. The proportion of PD-1-/TIM-3-positive cells is ~20% of CD4 + IL-10 + T cells and significantly exceeds the values of healthy individuals.