Background <p>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.</p> Methods <p>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.</p> Results <p>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 <i>in vitro–</i>generated-TAMs. SLAMF8 knockdown suppressed M2 polarization, whereas SLAMF8 overexpression promoted M2 polarization in <i>in vitro–</i>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.</p> Conclusions <p>SLAMF8 promotes macrophage M2 polarization and accelerates CD8 + T cell dysfunction, thereby facilitating the progression of GC.</p>

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SLAMF8 promotes tumor growth of gastric cancer by enhancing M2 polarization of tumor-associated macrophages

  • Yi Wu,
  • Xudong Zhang,
  • Zixiang Tang,
  • Fangjian Li,
  • Lin Wu,
  • He Zhou

摘要

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.