Cd48, a member of the signaling lymphocytic activation molecule family, is a glycosyl-phosphatidyl-inositol (GPI)-anchored cell-surface protein of the CD2 family. It participates in adhesion and activation of immune cells, and is expressed on various hematopoietic cells. Its expression can be regulated by viral and bacterial products as well as immune-associated proteins. CD48 binds to CD2 and 2B4, and through these interactions, it plays a role in multiple immune-related pathways, being a key player in immune system regulation [2,3,4].

In hepatocellular carcinoma (HCC), gene ablation of GDF15, which interacts with CD48 on regulatory T (Treg) cells, can convert an immunosuppressive tumor microenvironment to an inflammatory state. GDF15 promotes the generation of peripherally derived inducible Treg cells and enhances the suppressive function of natural Treg cells via CD48, downregulating STUB1, an E3 ligase that mediates forkhead box P3 protein degradation [1]. In non-small-cell lung cancer (NSCLC), CD48-positive NSCLC cells are more susceptible to natural killer cell-mediated cytotoxicity, as CD48-positive cells establish more stable contact with NK cells [5].

In conclusion, CD48 is crucial in immune cell adhesion and activation. Gene-knockout related studies, like GDF15 gene ablation in HCC mouse models, have revealed its role in tumor-associated immunosuppression. In NSCLC, its impact on NK-cell-mediated cytotoxicity shows its potential significance in cancer immunotherapy. These findings emphasize the importance of CD48 in understanding immune-related disease mechanisms and developing potential therapeutic strategies.