CD84 and the Tumour Microenvironment (TME)

April 6 2026 first review Maisey Zhao.pdfCD84 and the Tumour Microenvironment (TME) Maisey Zhao, University of Toronto Schools (UTS) Sun Life Gene Medical Science Institute Cancer Research Program Student, Toronto, Ontario, Canada Abstract CD84, or SLAMF5, is a member of the Signalling Lymphocytic Activation Molecule Family (SLAM), a family of immunoreceptors that play key roles in immune cell function, particularly in T and B cells, and regulating immune cell activities. It behaves as a homophilic adhesion molecule; by binding onto other CD84 molecules in neighbouring cells, the protein can mediate cell-to-cell interactions and regulate immune responses, including tolerance. Recent findings have continued to highlight CD84’s potential therapeutic target to reduce MDSCs and restore anti-tumour immunity in various autoimmune disorders and cancers, including multiple myeloma and triple-negative breast cancer, given its ability to help MDSCs accumulate in the tumour microenvironment and its suppression of anti-tumour immune responses. The protein is expressed on multiple immune cell types, including thymocytes (highest expression present in single positive cells), T cells, and follicular T helper (TFH) cells, activated B cells, macrophages, DC, platelets, basophils, mast cells, and eosinophils, and has shown great aptitude in immune evasion through enhancing regulatory B cell function, promoting myeloid-derived suppressor cell expansion, and upregulating immune checkpoint molecules like PD-L1 on the MDSCs, leading to T-cell exhaustion. Therapeutic methods with targeting CD84, such as monoclonal antibodies and CAR T-cell therapies, have shown promise in counteracting immunosuppression and improving treatment results, and highlights CD84’s significance as a prognostic biomarker and a novel target in cancer immunology. This review will explore CD84 and its role in the tumor microenvironment, including solid tumour and hematologic malignance (such as multiple myeloma), and discuss CD84 as a therapeutic target in cancer immunology as described in recent research findings. Keywords: CD84, tumour microenvironment, MDSC, PD-1/PD-L1, hematologic cancers, malignant cancers, solid tumours