Interactions between CLL cells and bystander cells that subsidize the formation of a tumor-supportive microenvironment. The molecular interactions of innate immune cells (macrophages, dendritic and nurse-like cells) and adaptive immune cells (B and T cells) have relevant effects, such as survival, immunosuppression, proliferation and signaling molecules (in blue) involved in the interactions of CLL cell. The response of CLL cells includes exhaustion of T cells, expansion, chemoattraction, immunosuppression, and immune evasion (in green) on innate and adaptive immune cells. However, IL-2 and IL-10 (in red) contribute to the autocrine self-renewal and survival of CLL cells. APRIL, a proliferation-inducing ligand; BAFF, B cell activating factor; BCR, B cell receptor; CCL, chemokine (C-C motif) ligand; CD, cluster of differentiation; CLL, chronic lymphocytic leukemia; CSF1R, colony-stimulating factor-1 receptor; CSF1, colony-stimulating factor-1; CXCL, chemokine (C-X-C motif) ligand; (TGF-β), Transforming growth factor beta; NAMPT, extracellular nicotinamide phosphoribosyltransferase; HMGB1, High mobility group box 1; IL, interleukin; MIF, mini zinc finger; PI3K/mTOR, phosphatidylinositol-3-kinase/mammalian target of rapamycin; TAM, tumor-associated macrophage; MHC, major histocompatibility complex; TNF, tumor necrosis factor; CCR, chemokine receptor; IDO, indoleamine 2,3-dioxygenase; PD-1, program cell death; IRF4, interferon regulatory factor; IFN, interferon.