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. 2021 Mar 26;13(7):1536. doi: 10.3390/cancers13071536

Figure 1.

Figure 1

Leukemic microenvironment supports survival of acute lymphoblastic leukemia (ALL) cells and their immune evasion through multiple interactions. Various cell populations shape the leukemic microenvironment. Regulatory T cells (Tregs) secrete inhibitory cytokines that suppress the cytotoxic activity of T cells and reduce macrophage phagocytosis. Granulocytic Monocyte Derived Suppressor Cells (G-MDSC) produce reactive oxygen species (ROS) that inhibit activity of T cells and natural killer (NK) cells. NK cells express low levels of natural cytotoxicity triggering receptor p46 (NKp46) activating receptor, while ALL cells downregulate major histocompatibility complex class I-related chains A/B (MIC-A/B)-a ligand for natural killer group 2 member D (NKG2D) activating receptor. ALL also drives NK cell dysfunction by secreting immunosuppressive transforming growth factor beta (TGF-β). Mesenchymal stem cells (MSCs) secrete chemokines, e.g., C-X-C chemokine ligand 12 (CXCL12), which binds C-X-C chemokine receptor type 4 (CXCR4) and promotes ALL engraftment into the vascular niche. Furthermore, MSCs protect ALL cells against the treatment by secretion of galectin-3, which activates the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway. MSCs also secrete metabolites, such as asparagine, which reduces the cytotoxicity of L-asparaginase. Non-classical (CD16+) monocytes infiltrate the leukemic microenvironment and are thought to be involved in ALL cells protection. Macrophages from the leukemic niche acquire immunosuppressive properties and secrete tumor-promoting cytokine TGF-β. Their phagocytic activity is reduced by the interaction of signal regulatory protein α (SIRPα) with cluster of differentiation 47 (CD47)—a “do not eat me signal” expressed by leukemic cells. The figure was created in BioRender (https://biorender.com/; accessed on 27 February 2021). Other abbreviations: CD200, cluster of differentiation 200; CD200R, CD 200 receptor; G-MDSC, Granulocytic Monocyte Derived Suppressor Cells; IL-10, Interleukin 10; TIM3, T-cell immunoglobulin domain and mucin domain 3.