BACKGROUND: The signaling lymphocytic activation molecule family member 8 (SLAMF8) is predominantly expressed on the surface of macrophages and participates in modulating tumor immune microenvironment. However, the role of SLAMF8 in tumor-associated macrophages (TAMs) in gastric cancer (GC) remains unclear. METHODS: SLAMF8 expression and its association with patient prognosis were analyzed using various online databases. CCK-8 and EdU assays were used to assess GC cell proliferation. A xenograft tumor model was used to assess the in vivo functional role of SLAMF8. RESULTS: SLAMF8 expression was markedly increased and correlated with an unfavorable prognosis in GC. Additionally, SLAMF8 was primarily expressed in macrophages in GC tissues and increased in in vitro-generated-TAMs. SLAMF8 knockdown suppressed M2 polarization, whereas SLAMF8 overexpression promoted M2 polarization in in vitro-generated TAMs. SLAMF8 facilitates TAM-like polarization by coordinately inhibiting NF-κB activation and activating the JAK2/STAT3 signaling pathway. Furthermore, SLAMF8-overexpressing TAMs enhanced the growth of MKN-45 cells both in vitro and in vivo and impaired CD8 + T cell function. CONCLUSIONS: SLAMF8 promotes macrophage M2 polarization and accelerates CD8 + T cell dysfunction, thereby facilitating the progression of GC.
Wu et al. (Sat,) studied this question.