Interleukin-1 receptor accessory protein (IL-1RAP): A magic bullet candidate for immunotherapy of human malignancies

IL-1, plays a role in some pathological inflammatory conditions. This pro-inflammatory cytokine also has a crucial role in tumorigenesis and immune responses in the tumor microenvironment (TME). IL-1 receptor accessory protein (IL-1RAP), combined with IL-1 receptor-1, provides a functional complex for binding and signaling. In addition to the direct role of IL-1, some studies demonstrated that IL1-RAP has essential roles in the progression, angiogenesis, and metastasis of solid tumors such as gastrointestinal tumors, lung carcinoma, glioma, breast and cervical cancers. This molecule also interacts with FLT-3 and c-Kit tyrosine kinases and is involved in the pathogenesis of hematological malignancies such as acute myeloid lymphoma. Additionally, IL-1RAP interacts with solute carrier family 3 member 2 (SLC3A2) and thereby increasing the resistance to anoikis and metastasis in Ewing sarcoma. This review summarizes the role of IL-1RAP in different types of cancers and discusses its targeting as a novel therapeutic approach for malignancies.