Cd84, also known as SLAMF5, is a member of the SLAM family of cell-surface immunoreceptors. It functions as a homophilic adhesion molecule, and its signaling can either activate or inhibit leukocyte function depending on cell type, activation, or differentiation stage. Cd84-mediated signaling regulates diverse immunological processes, including T cell cytokine secretion, natural killer cell cytotoxicity, monocyte activation, autophagy, T:B interactions, and B cell tolerance at the germinal center checkpoint [1].

In multiple myeloma, down-regulation or blocking of Cd84 reduces myeloid-derived suppressor cell (MDSC) accumulation, leading to elevated T cell activity and reduced tumor load, suggesting it as a potential therapeutic target [2]. In acute myeloid leukemia, Cd84 down-regulation disrupted leukemia cell proliferation, clonogenicity, and engraftment in both human cell lines, patient-derived xenograft cells, and mouse models, highlighting its role as a survival factor [4]. In Mycobacterium tuberculosis-infected Cd84-deficient mice, there was improved bacterial clearance and longer survival, indicating that Cd84 likely leads to T and B cell immunosuppression during pathogenesis [3].

In conclusion, Cd84 plays a crucial role in regulating immune cell functions and is involved in various disease conditions such as cancer and infectious diseases. Studies using gene-knockout mouse models have revealed its significance in processes like cell survival, immunosuppression, and pathogen clearance, providing potential therapeutic implications for these diseases.

References:

1. Cuenca, Marta, Sintes, Jordi, Lányi, Árpád, Engel, Pablo. 2018. CD84 cell surface signaling molecule: An emerging biomarker and target for cancer and autoimmune disorders. In Clinical immunology (Orlando, Fla.), 204, 43-49. doi:10.1016/j.clim.2018.10.017. https://pubmed.ncbi.nlm.nih.gov/30522694/

2. Lewinsky, Hadas, Gunes, Emine G, David, Keren, Rosen, Steven, Shachar, Idit. 2021. CD84 is a regulator of the immunosuppressive microenvironment in multiple myeloma. In JCI insight, 6, . doi:10.1172/jci.insight.141683. https://pubmed.ncbi.nlm.nih.gov/33465053/

3. Zheng, Nan, Fleming, Joy, Hu, Peilei, Bi, Lijun, Zhang, Hongtai. 2022. CD84 is a Suppressor of T and B Cell Activation during Mycobacterium tuberculosis Pathogenesis. In Microbiology spectrum, 10, e0155721. doi:10.1128/spectrum.01557-21. https://pubmed.ncbi.nlm.nih.gov/35196822/

4. Zhu, Yinghui, Murtadha, Mariam, Liu, Miaomiao, Williams, John C, Pichiorri, Flavia. 2025. Identification of CD84 as a potent survival factor in acute myeloid leukemia. In The Journal of clinical investigation, , . doi:10.1172/JCI176818. https://pubmed.ncbi.nlm.nih.gov/40198133/