Role and mechanism of Pim-2 kinase inhibitor-induced immunogenic cell death in multiple myeloma

Background : Immune dysfunction is a major component in the pathogenesis of multiple myeloma (MM), and restoring antimyeloma immunity has become a key research direction. Methods : This study demonstrates, through in vivo and in vitro experiments, whether and how Pim-2 kinase inhibitors induce immunogenic cell death in MM. Results : Pim-2 kinase inhibitors upregulated IRE1 phosphorylation and promoted XBP1 and CHOP transcription, thereby mediating endoplasmic reticulum (ER) stress in MM cells. ER stress and increased reactive oxygen species levels promoted damage-related molecular pattern expression and immunogenic cell death in MM cells. Furthermore, Pim-2 kinase inhibitor-treated MM cell lines upregulated the expression of activation molecules on the surface of dendritic cells (DCs) in patients with MM, stimulated T lymphocyte differentiation from naïve T cells to effector memory T cells, and promoted the expression of T lymphocyte functional molecules. In vivo , Pim-2 kinase inhibitors stimulated human DC maturation and activated functional T lymphocytes. Conclusion : These data contribute to our knowledge about how Pim-2 kinase inhibitors regulate antimyeloma immunity and provide justification for applying Pim-2 kinase inhibitors in MM treatment.