Fig. 4

Potential mechanisms of Selinexor on tumor cells and microenvironment of EMM to promote CAR-T function. Left part: Without Selinexor, CAR-T cell function can be restricted by the insufficient BCMA expression on myeloma cells, as well as the tumor microenvironment, including physical barriers of tumor (vascular and extracellular matrix disorder), and immunosuppressive factors (e.g., TAM, MDSC, Treg, and their secreted cytokines). Right part: After the use of Selinexor, the BCMA expression on myeloma cells can be upregulated, repolarization of M2-like macrophages is promoted and the number of M1-like macrophages increases. For the immunosuppressive cells such as CAFs and Treg, and suppressive cytokines such as TGF-β and NFκB, the influence of Selinexor remains to be explored. Selinexor might have the potential to facilitate CAR-T cell infiltration and expansion if remodulation of the immunosuppressive microenvironment is possible. Abbreviations: CAF, cancer-associated fibroblast; DC, dendritic cell; FGF, fibroblast growth factor; IL, interleukin; NF, nuclear factor; MDSC, myeloid-derived suppressor cells; MM, multiple myeloma; NK, natural killer; TAM, tumor-associated macrophages; TGF, tumor growth factor; Treg, regulatory T cells; VEGF, vascular endothelial growth factor