Optimizing iNKT-driven immune responses against cancer by modulating CD1d in tumor and antigen presenting cells

Two major antigen processing pathways represent protein Ags through major histocompatibility complexes (MHC class I and II) or lipid Ags through CD1 molecules influence the tumor immune response. Invariant Natural Killer T cells (iNKT) manage a significant role in cancer immunotherapy. CD1d, found on antigen-presenting cells (APCs), presents lipid Ags to iNKT cells. In many cancers, the number and function of iNKT cell are compromised, leading to immune evasion. Additionally impaired motility of iNKT cells may contribute to poor tumor prognosis. Emerging evidences suggest that CD1d, itself also influences cancer progression. Patient databases further highlight the importance of CD1d expression in different cancers and its correlation with patient survival outcomes. The ability of iNKT cells to activate and enhance the immune response renders them an attractive target for cancer immunotherapy. This review discusses all the possible ways of cancer immune evasion and restoration of immune responses mediated by CD1d-iNKT interactions.