Fig. 4

SLAMF receptors modulate cancer progression. The regulatory roles of SLAMF receptors in cancer depend on both the specific types of SLAMF receptors and the type of cancer. a The homophilic interaction of SLAMF3 between leukemia cells and T cells contributes to activating T cells, and the SLAMF2-SLAMF4 interaction between them initiates cytotoxic anti-tumor effects mediated by T cells. However, the homophilic interaction of SLAMF7 between NK cells and leukemia cells inhibits the tumor killing effects mediated by NK cells. Moreover, SLAMF5 expressed on leukemia cells promote tumor progression by upregulating the PD-1 expression on effective T cells as well as the PD-L1 expression on leukemia cells. b The homophilic interaction of SLAMF7 between NK cells and MM cells or T cells and MM cells inhibits the anti-tumor responses mediated by NK cells or T cells. SLAMF3 expressed on MM cells also promotes tumor progression by activating the RASAL3-RAS-Erk signaling pathway. Moreover, other immune cells infiltrated in TME contributes to MM progression. SLAMF7⁺Treg cells can inhibit the function of T cells, and SLAMF5⁺MDSCs can induce immunosuppressive signaling pathways. c The interaction of SLAMF4 and SLAMF2 expressed on NK cells and lymphoma cells respectively enhance the anti-tumor effects mediated by NK cells. In addition, the activation of SLAMF8 expressed on lymphoma cells promote cancer progression, but the specific mechanisms are unknown. d In CRC, the interaction of SLAMF4 and SLAMF2 between NK cells and target tumor cells enhances cytotoxic effects. However, SLAMF8⁺macrophages and SLAMF4⁺MDSCs promote tumor progression. e The homophilic combination of SLAMF3 expressed on HCC cells and adjacent hepatocytes can promote tumor apoptosis while inhibiting cancer progression. Moreover, SLAMF7⁺ macrophages can inhibit MAPK-ATF-2-mediated CCL2 production, which further inhibit the formation and migration of type 2 macrophages. In contrast, the SLAMF2 stimulated by growth differentiation factor 15 can promote tumor progression by inhibiting ERK-AP-1 signaling pathway. f The combination of SLAMF4 and SLAMF2 respectively expressed on NK cells and melanoma cells enhances killing effects, which can be impaired by their homophilic SLAMF7 combination. The red lines represent the positive roles of SLAMF receptors in inhibiting cancer progression, while the purple lines indicate their negative roles in cancer progression. Abbreviation: MM, multiple myeloma; HCC, hepatocellular carcinoma; NSCLC, non-small cell lung cancer; CRC, colorectal cancer; PD-1, programmed cell death protein-1; PD-L1, programmed cell death protein-1-ligand-1; Treg, regulatory T; MDSC, myeloid-derived suppressor cell; RAS, rat sarcoma; RASAL3, RAS protein activator like 3; ERK, extracellular signal-regulated kinase; AP-1, activator protein 1; MAPK, mitogen-activated protein kinase; ATF-2, activating transcription factor 2; CCL, C–C motif chemokine ligand 2. The figure is created with BioRender.com