Immunoglobulin‑like transcript 4 and human leukocyte antigen‑G interaction promotes the progression of human colorectal cancer

Abstract

Immunoglobulin-like transcript (ILT) 4, a negative regulator of immune response in allograft rejection, autoimmunity and infectious diseases, has recently been determinedtoserveimportantrolesintumordevelopment.Inthe present study, the co-expression of ILT4 and human leukocyte antigen-G (HLA-G) in tissues of human primary colorectal cancer (CRC) was revealed, and its association with older age, advanced stage, regional lymph node involvement and poor overall survival time was identified. In CRC cell lines, ILT4 and HLA-G co-expression and their autocrine regulation was demonstrated. ILT4 interference affected HLA-G expression and regulated the cell proliferation, invasion and migration of CRC. HLA-G fusion protein treatment also increased ILT4 expression in a dose-dependent manner, thereby activating protein kinase B (AKT) and extracellular signal-regulated kinase (ERK) signaling, and facilitating the proliferation, migration and invasion of CRC cells. Additionally, the AKT and ERK activation, and CRC cell malignant characteristics induced by HLA-G may be suppressed by blocking ILT4. The present results indicated that the interaction of ILT4 and its ligand HLA-G promotes CRC progression through AKT and ERK signal activation, providing a novel strategy of blocking ILT4/HLA-G for the treatment of CRC.