SLAMF6 Enhances the Efficacy of Anti‐PD‐L1 Immunotherapy in CRC Through the STAT1/CXCL10 Signaling Axis

Abstract

ABSTRACT As a T‐cell receptor co‐stimulatory protein, signaling lymphocyte activation molecule family 6 (SLAMF6) is a member of the immune cell activating receptor family and is expressed on T cells, B cells, natural killer cells (NK cells), and tumor cells. To date, the biological functions and clinical significance of SLAMF6 in certain solid tumors remain to be elucidated. We analyzed the transcriptional expression pattern of SLAMF6 and its relationship with clinical outcomes using clinical specimens and pancancer databases. Next, multispectral immunofluorescence was applied to assess the correlation between SLAMF6 expression and CD8+ T‐cell activation and infiltration in clinical samples, with additional validation through immune‐infiltration analysis. In parallel, using a colorectal cancer xenograft model, we examined how upregulation of SLAMF6 combined with immune‐checkpoint blockade (anti‐PD‐L1) influences immunotherapy efficacy. Ultimately, our findings indicate that SLAMF6 modulates CD8+ T‐cell activation and infiltration through the STAT1/CXCL10 axis, thereby enhancing the recruitment of these effector cells to tumor sites.