ILT2 and ILT4, which are expressed on myeloid cells in the tumor microenvironment, are implicated in suppressing the anti-tumor immune response and may represent checkpoints that enable tumors to evade immune detection. Suppressive myeloid cells enriched with ILT2 and ILT4 receptors are upregulated in certain cancer types, while ILT2 is also expressed on natural killer (NK) cells, B cells and a subset of highly cytolytic T cells.
Of note, ILT2 and ILT4 are upregulated on macrophages in the tumor microenvironment of certain cancer patients who are non-responders to T cell checkpoint inhibitor therapy and, therefore, may play a role in tumor resistance to T cell checkpoint inhibitors. Reversing myeloid suppression, or myeloid reprogramming, represents a promising new therapeutic area of immuno-oncology.