Targeting CD38 Suppresses Induction and Function of T Regulatory Cells to Mitigate Immunosuppression in Multiple Myeloma.

摘要: Purpose: We study CD38 levels in immunosuppressive CD4+CD25highFoxp3+ Tregs and further define immune modulating effects of a therapeutic monoclonal antibody (mAb) Isatuximab (Isa)/SAR650984 multiple myeloma (MM). Experimental Design: evaluated percentages CD38-expressing subsets from normal donors MM patients. PBMCs were then treated with Isa or without Lenalidomide (Len) Pomalidomide (Pom) to identify their impact on percentage activity CD4+CD25- T cells (Tcons). investigated the mechanism increased patients ex vivo cocultures Tcons. Results: expression is higher than Tcons versus donors. CD38high are by Len Pom. preferentially decreases Treg increases Tcon frequencies, which enhanced Pom/Len. reduces Foxp3 IL10 restores proliferation function It augments cell lysis CD8+ natural killer cells. Coculture significantly induces (iTregs), express even CD38, CD25, FoxP3 Tregs. This associated elevated circulating CD38+ vs. Conversely, cell- bone marrow stromal cell-induced iTreg inhibiting both cell-cell contact TGFBeta/IL10. Finally, correlate differential inhibition vs donors. Conclusions:: Targeting can block thereby restore effector against MM.