Signaling lymphocytic activation molecule family member 8 (SLAMF8) / B-lymphocyte activator macrophage expressed/CD353 is a member of the CD2 family. SLAMF8 suppresses macrophage function but enhances the growth of neoplastic mast cells via SHP-2. In this study, we found that some anaplastic large cell lymphoma (ALCL) samples were immunohistochemically positive for SLAMF8. However, we found no significant differences between SLAMF8-positive and SLAMF8-negative ALCL samples with respect to age, gender, site, or prognosis. We also identified SLAMF8 expression in ALCL cell lines, Karpas299, and SU-DHL-1. SLAMF8 knockdown decreased the activation of SHP-2 and the growth of these cell lines, and increased the apoptosis of these cell lines. In addition, we observed the interaction between SLAMF8 and SHP-2 in these cell lines using the DuoLink in situ kit. Taken together, these results suggest that SLAMF8 may enhance the growth of ALCL via SHP-2 interaction. The signaling lymphocytic activation molecule (SLAM) family of receptors is expressed by and regulates the functions of immune cells 1,2. SLAM family member 8 (SLAMF8)/B-lymphocyte activator macrophage expressed/ CD353 is a cell-surface protein and a member of the CD2 family 1,2. However, its ligand has not yet been identified. SLAMF8 is a potent marker for tumor infiltrating T cells. SLAMF8 are abundantly expressed in T cells infiltrating in pediatric cancers and Epstein-Barr virus-positive gastric cancers, and thought to be a marker for potential immunotherapy targets 3,4. In addition, SLAMF8 is expressed by and suppresses macrophage the function of human macrophage 5,6. SLAMF8 is also expressed by and enhances the growth of human neoplastic mast cells 7. SLAM family signaling is generally mediated by SLAM-associated protein (SAP) or Ewing's sarcoma-associated transcript 2 (EAT-2) in lymphocytes and macrophage cells 1,2 , although SLAMF8 signaling is mediated by the Src homology region 2 domain-containing phosphatase-2 (SHP-2) in human mast cells 7. To the best of our knowledge, no studies have explored the expression of SLAMF8 in anaplastic large cell lymphoma (ALCL). ALCL cells are typically large, have abundant cytoplasm and horseshoe-shaped nuclei, and are positive for CD30 on the cell membrane and in the Golgi region 8. The expression of anaplastic lymphoma kinase (ALK) is clinically important, and the prognosis of ALK-positive ALCL is favorable compared to ALK-negative ALCL. There are three subtypes of ALCL: ALK-positive, ALK-negative, and primary cutaneous ALCL. In this study, we analyzed the expression and function of SLAMF8 in ALCL clinical samples and cell lines. Results Human ALCLs express SLAMF8 mRNA and protein. We examined the expression of SLAMF8 mRNA and protein in the human ALCL cell lines SU-DHL-1 and Karpas299 using RT-PCR and immunoblotting, respectively. Both cell lines expressed SLAMF8 mRNA and protein (Fig. 1A,B). Both cell lines showed ALK translocation 9,10 and we treated these with an ALK inhibitor, crizotinib 11. The administration of cr...