CD4+GM-CSF+ T Cells in Multiple Myeloma Patients

The function of granulocyte-macrophage colony-stimulating factor (GM-CSF) in the development of multiple myeloma (MM) is not clearly elucidated. The aim of this study was to investigate the content of CD4+ helper T cells producing GM-CSF and their possible relationship with monocytic myeloid-derived suppressor cell (M-MDSC) counts in MM patients. The study included 54 MM patients and 10 matched healthy donors. The content of GM-CSF-producing CD4+ T cells and malignant plasma cells (PCs) was assessed by flow cytometry. In vitro expansion of CD4+GM-CSF+ T cells was studied after stimulation with anti-CD3/CD28 or a combination of IL-2, IL-7, and IL-15. CD4+GM-CSF+ T cell counts were higher in MM patients compared to healthy donors. CD4+GM-CSF+ T cell frequency did not differ in the patients achieving remission and the ones with progressive disease. The increase was shown only in patients in remission prior to the conditioning with high-dose melphalan. The relative count of CD4+GM-CSF+ T cells at the engraftment also remained stable. Circulating CD4+GM-CSF+ T cells are inversely correlated with MM PC burden. There were no associations between CD4+GM-CSF+ T cells and M-MDSC counts both before the conditioning and after autologous hematopoietic progenitor cell transplantation. In an in vitro assay, CD4+GM-CSF+ T cells exhibited enhanced proliferation when stimulated with homeostatic cytokines, but not with aCD3/CD28, contrasting with the cultures derived from patients with autoimmune diseases. We did not find evidence supporting a tumor-promoting role for CD4+GM-CSF+ T cells in MM.