SLAMF8 (BLAME) as a novel immune checkpoint: Implications for inflammation, autoimmunity, and oncology

Abstract

SLAMF8 is a structurally distinct member of the SLAM receptor family, lacking classical intracellular signaling motifs yet exerting broad immunomodulatory functions. Predominantly expressed in myeloid-derived cells, SLAMF8 orchestrates a spectrum of immune responses—modulating oxidative burst, phagocytosis, cellular trafficking, and receptor expression—through noncanonical signaling pathways. Its regulatory footprint spans both innate and adaptive immunity, influencing macrophage polarization, T cell development, and antigen presentation. Recent findings illuminate SLAMF8's pivotal involvement in disease contexts marked by chronic inflammation, immune dysregulation, and malignancy. Elevated SLAMF8 expression is linked to tumor progression, immune evasion, and resistance to immunotherapies in various cancers, while its dysregulation contributes to autoimmunity, cardiovascular injury, and infectious disease pathogenesis. Beyond its functional roles, SLAMF8 is emerging as a versatile biomarker—reflecting immune microenvironments, predicting treatment outcomes, and potentially guiding therapeutic strategies. This review synthesizes current insights into SLAMF8’s biological roles and clinical relevance, positioning it as a compelling interface between immune homeostasis and disease. As research deepens, SLAMF8 may redefine therapeutic approaches across oncology, immunology, and regenerative medicine.