ILT4 functions as a potential checkpoint molecule for tumor immunotherapy

Immune checkpoint blockade therapy targeting CTLA4 and PD-1/PD-L1 is a promising strategy in the treatment of different types of cancers. However, the clinical success rates of these therapies are still moderate and varied among cancer types. Therefore, identification of alternative and novel checkpoint molecules or interrupting tolerogenic pathways is urgently needed for successful tumor immunotherapy. Immunoglobulin-like transcript 4 (ILT4) is as an immunosuppressive molecule predominantly expressed in myeloid cells, including monocytes, macrophages, dendritic cells and granulocytes. Recent studies revealed that ILT4 is also enriched in tumor cells and stroma cells in the tumor microenvironment of various malignancies, modulating the biological behaviors of tumor cells and promoting their immune escape. However, the underlying mechanisms responsible for ILT4-mediated tumor development and progression are still poorly understood. In this review, we explore the functional role of ILT4 as a novel checkpoint molecule in cancers. We specifically discuss the mechanisms mediated by ILT4 for controlling tumor malignant behaviors, impairing effector anti-tumor immune responses, and sustaining the tumor suppressive microenvironment. We also highlight the potential role of ILT4 as a novel immune checkpoint target for tumor immunotherapy. Improved understanding of these issues is critical for elucidation of the role of ILT4 in tumor pathogenesis and should open new avenues for cancer immunotherapy specifically targeting this novel and alternative checkpoint molecule.