The role of NK cell receptor-expressing cell on anti-leukemia/cancer immunological effect

Abstract

NK cells recognize MHC class I molecules and inhibit the killing of target cells that have self MHC class I molecules through their inhibitory receptors. Therefore inhibitory NK receptor negatively regulate NK cell functions, including target cell lysis, through their binding to MHC class I molecules. The development of leukemia and malignant tumors might be induced as a consequence of the failure of immune surveillance. Leukemic cells and tumor cells can escape from immune recognition by cytotoxic T cells because of the low expression level of tumor antigen and/or HLA class I molecules. In such cases, non-tumor antigen-restricted cytotoxic cells such as NK cells and NK receptor-expressing cells may be important to overcome tolerance in the tumorbearing host. Donor allogeneic NK cells can attack patient's leukemic cell resulting in the enhancement of graft-versus-leukemia（GVL）effect and at the same time attack host antigen-presenting cells resulting in the suppression of graft-versus-host disease（GVHD）in allogeneic stem cell transplantation with Killer cell immunoglobulin-like recepto（r KIR）-ligand mismatch donor. Therefore, NK cell and KIR incompatibility may have an important role in the clinical outcome of immunological cell therapy such as allogeneic stem cell transplantation for not only hematological malignancies but also solid cancers.