Fig. 3

The mechanism of CD19+ relapse in BM microenvironment. a Main interaction between negative regulatory cells, tumor cells and immune effector cells in BM microenvironment. Tregs, MDSCs and TAMs suppress CTLs, DCs, NK cells and T cells by cytokines, enzymes and cell-cell interactions. Negative regulatory cells and tumor cells attract and improve each other’s recruitment, differentiation and expansion. Tregs: regulatory T cells; MDSCs: myeloid-derived suppressor cells; TAMs: tumor associated macrophages; IDO: indoleamine-2, 3-dioxygenase; CTLs: cytotoxic T cells; DCs: dendritic cells; NK cells: natural kill cells; TGF-β: transforming growth factor β. b The negative regulation checkpoint in BM microenvironment. The PD-1/PD-L1 pathway between tumor cells and MDSCs, T cells, TAMs inhibits the proliferating of T cells and transforms T cells into induces Tregs or induces apoptosis. The CTLA-4/B7 pathway suppresses APCs while activates Tregs. (Tregs: regulatory T cells; iTregs: induced Tregs; TAMs: tumor associated macrophages; APCs: antigen-presenting cells; MDSCs: myeloid-derived suppressor cells; PD-1: programmed death-1; PD-L: programmed cell death 1 ligand)