Targeting ILT4 to Improve Immunotherapy Efficacy in Solid Tumour: From Bench to Bedside

Immunotherapy, especially immune checkpoint inhibitors (ICIs), has greatly changed the paradigm of cancer treatment in the past decade. However, the efficacy of ICIs in solid tumors is still limited. Even in patients with high PD-L1 expression, the response rate is less than 40%. The immunosuppressive tumour microenvironment (TME) represents a major cause of ICI hyporesponsiveness due to its inhibition on effective T-cell trafficking and immunity. Exploring novel immunotargets and developing combination therapeutics represent promising strategies to improve tumor response to immunotherapy. Immunoglobulin-like transcript (ILT) 4 is a classical inhibitory molecule in myeloid cells. Recently, ILT4 expression was discovered in tumour cells and multiple immunocytes in the TME, functionally inducing tumour growth, metastasis, and immune escape. Our group proposed ILT4 as a novel checkpoint molecule for tumour immunotherapy in 2018. In the past 5 years, translational research on ILT4 has made remarkable advances. Here, we update recent findings on ILT4 function in the TME, summarize the translational research on the development of therapeutic ILT4 antibodies, and highlight emerging clinical trial data supporting the role of ILT4 blockade in improving immunotherapy efficacy.