Bone marrow B lymphocytes in multiple myeloma and MGUS: Focus on distribution of naïve cells and memory subsets

Genetic variants of CTLA4 are associated with clinical outcome of patients with multiple myeloma

“…The immune dysfunction and neoplastic evasion in MM is facilitated by multiple cytokine and cellular signaling pathways, which decrease immune effector cell function and determine a suppressive bone marrow microenvironment (2). This impaired cellular immunity is mediated by an increased number and functional impairment of dendritic cells (21), altered circulating CD4/CD8 ratio (22), decreased Th1/Th2 ratio (23), increased number of Treg (24), lower level of naïve and transitional B cells subsets in the bone marrow (25), increased number of myeloid derived suppressor cells (MDSC) in the blood and in the bone marrow (26), and enhanced expression of inhibitory ligands such as programmed cell death ligand 1 (PDL-1) by myeloma and bone marrow microenvironment cells, together with an increased expression of PDCD1 and CTLA4 on tumor infiltrating T cells (27,28). The immunosuppressive state in MM determines important clinical implications, there is increasing evidence that the resistance to bispecific T cell engagers (TCEs) is closely related to immunosuppressive tumor microenvironment (29) in the bone marrow of TCE-receiving patients predicts response failure in MM.…”