We observed increased expression of TIM-3, LAG-3, CTLA4, and 2B4 on both CD8 and CD4 T cells in myeloma-bearing mice, and anti-myeloma synergy occurred when the PD-1/PD-L1 axis was blocked in combination with blocking TIM-3, LAG-3, or CTLA4. Here, CD274 is linked to plasma cell myeloma.