SLAM Family Receptors in Cancer

Abstract

The tumour microenvironment (TME) is a strongly immunosuppressive tissue in which dysfunctional immune cells support tumour cell survival and immune evasion. This literature review focuses on the function of the nine-member signalling lymphocytic activation molecule (SLAM) receptor family (SLAMF) in the TME, with particular emphasis on SLAMF5 (CD84) and SLAMF7 (CD319). The expression patterns and signalling mechanisms of these receptors are discussed across key immune cell populations, including natural killer cells, T cells, dendritic cells, regulatory T cells, tumour-associated macrophages, and myeloid-derived suppressor cells. While SLAMF7 is generally associated with enhanced NK cell cytotoxicity and can support antitumour CD8⁺ T-cell responses, SLAMF5 has been consistently linked to immunosuppressive activity, primarily through promoting MDSC accumulation and upregulation of PD-L1 expression. The clinical relevance of SLAMF7 is underscored by elotuzumab, an anti-SLAMF7 monoclonal antibody which is already in use in the ELOQUENT-2 and ELOQUENT-3 clinical trials for the treatment of relapsed or refractory multiple myeloma.