In the immune system, CD48 was the first discovered receptor for growth differentiation factor 15 (GDF15), and studies have shown that upregulated expression of GDF15 in HCC can regulate the suppressive function of natural Tregs (nTregs) through interaction with the CD48 receptor on T cells and transcriptional gene silencing mechanisms [44]. This evidence concerns the gene GDF15 and hepatocellular carcinoma.