SPP1 and neoplasm: M2-like TAMs express various ligands for T-cell immune checkpoints, such as PD-L1 (binding to PD-1), CD80 and CD86 (binding to CTLA4), NECTIN2/CD112 and PVR/CD155 (binding to TIGIT), LGALS9/Galectin-9 (binding to TIM-3), TNFRSF14/HVEM (binding to BTLA), and SPP1 (binding to CD44), thereby enhancing the immunosuppressive tumor microenvironment [35].