The Apelin/APLNR system modulates tumor immune response by reshaping the tumor microenvironment

Apelin is an endogenous ligand of the Apelin receptor (APLNR), a seven-transmembrane G protein-coupled receptor, which is widely distributed in human tissue. The Apelin/APLNR system is involved in regulating several physiological and pathological processes. The Apelin expression is increased in a variety of cancer and the Apelin/APLNR system could regulate the development of tumors through mediating autophagy, apoptosis, pyroptosis, and other biological processes to regulate tumor cell proliferation, migration, and invasion. The Apelin/APLNR system also participates in immune response and immune regulation through PI3K-Akt, ERK-MAPK, and other signal pathways. The latest research points out that there is a negative regulatory relationship between APLNR and immune checkpoint PD-L1. In this review, we outline the significance of the Apelin/APLNR signaling pathway in tumorigenesis and its immune regulation. These endeavors provide new insights into the translational application of Apelin/APLNR in cancer and may contribute to the promotion of more effective treatments for cancers.