SLAMF6 is a self-ligand receptor of the SLAM family that modulates immune cell activation through homo- or heterotypic cell-cell interactions 1. In T cells, SLAMF6 functions as an inhibitory receptor triggered by cis homotypic interactions at the T cell surface, suppressing T cell activation independently of tumor cell expression 2. SLAMF6 marks stem-like or progenitor-exhausted T (Tpex) cells that retain proliferative capacity and self-renewal potential, distinguishing them from terminally exhausted T cells 34. High SLAMF6 expression correlates with better prognosis in melanoma and breast cancer, associated with enhanced effector function and TCF7 expression 4. SLAMF6 also promotes Th17 differentiation through recruitment of RORC to the IL-17 promoter 1 and maintains intestinal Th17 cells as reservoirs for pathogenic effector T cell generation during autoimmunity 1. Clinically, aberrant SLAMF6 expression on AML cells serves as an immune escape mechanism in 60% of cases, and blocking SLAMF6 dimerization with antibodies restores T cell killing 5. SLAMF6 thus represents a dual-function molecule: marking therapeutic T cell populations while also enabling tumor immune evasion, positioning it as a promising immunotherapy target.