The failure of immune checkpoint blockade in multiple myeloma with PD-1 inhibitors in a phase 1 study

PD1 blockade enhances cytotoxicity of in vitro expanded natural killer cells towards myeloma cells

“…One recent phase I study in MM demonstrated that PD1 blocking by anti-PD1 antibody did not show significant treatment benefit [66]. This highlights that PD1 blocking based-immunotherapies need to be further improved.…”

Osteoclasts promote immune suppressive microenvironment in multiple myeloma: therapeutic implication

“…Specially, the expression of PD-L1 is much higher in OCs than in MM cells. PD-L1 expression in OCs, like 35 A recent report suggests that PD-L1 expression by infiltrating cells is more predictive of response to PD-1 pathway blockade than PD-1 expression on the tumor cells. 36 Importantly, we show that OCs express PD-L1 to induce immune suppression, thereby our data suggest potential effects of PD-L1 inhibitors in MM.…”

Activation of NK cells and disruption of PD-L1/PD-1 axis: two different ways for lenalidomide to block myeloma progression

“…Furthermore, NK and T cells stimulated with an anti-PD-1 antibody CT-011 restored the cytolytic ability of NK to kill target cells [46, 50, 54, 55]. Additionally, clonal T cells in MM can be hypo-responsive and fail to respond to several cytokines [64, 65]. Interestingly, these T-cell clones isolated from MM patients have normal TCR signaling but a defective p-SMAD pathway, which suppress cell proliferation.…”

“…Interestingly, these T-cell clones isolated from MM patients have normal TCR signaling but a defective p-SMAD pathway, which suppress cell proliferation. In particular, these T-cell clones displayed low levels of PD-1, which could explain their telomere-independent senescence [64, 65]. These results point out to the fact that PD-1 low T-cell clones fail to be fully activated by an anti-PD-1 therapy in MM, leading to a partial response in MM patients [65, 66].…”