CD4 and neoplasm: LAG-3, also known as CD223, is a single-pass transmembrane glycoprotein and is structurally homologous to CD4.44 LAG-3, with a higher affinity than CD4, can negatively regulate conventional CD4+ T cells through competitively binding to major histocompatibility complex class II (MHC II) on APC cell surface.45–47 On the other hand, LAG-3 expressing NK cells and CD8+ T cells can be affected through binding with LSECtin on liver cells and many tumour cells.48 Despite three decades of research, we still have many unanswered questions about the structure and function of LAG-3.