Fig. 5

Summary of single-cell studies in leukemic TME. (1) Immunosuppressive CD206⁺ and CX3CR1⁺ DC were found in AML TME. CD206⁺ DC recruits Treg by TNFSF8 upregulation and CX3CR1⁺ DC suppresses T-cells by increasing ligands of PDCD1 mediating T-cell suppression (CD274, PDLD2GH2) [81]. (2) Suppressive MS4A6A^high M2 macrophages were enriched in AML TME and showed Treg recruiting and suppressive signaling function [81]. (3) M2 macrophages increased fatty acid oxidation and NAD⁺ generation (NAMPT, EXOC5) and decreased phagocytosis ability in AML TME [83]. Exposure of AML blasts to M2 macrophage resulted in increased mitochondrial metabolism and survival, which is in part due to mitochondrial exchange [83]. (4) Non-classical (CD16⁺) monocytes were recruited for repairing the vascular remodeling effect of B-ALL. High-level of CD16⁺ monocytes are poor prognosis predictive [36]. (5) IL-10 mediated the PD-1^int and PD-1^high subtypes of T-cell, preventing the excessive activation and exhaustion of T-cells in CLL TME [91]. (6) Senescence-like T-cells (marked by CD57 and γ-H2AX) were found in AML TME, correlating with impaired T-cell cytotoxic effect and poor clinical outcomes [87]