Overcoming Resistance to Natural Killer Cell Based Immunotherapies for Solid Tumors

摘要: Despite advances in the diagnostic and therapeutic modalities, prognosis of several solid tumor malignancies remains poor. Different factors associated with tumors including a varied genetic signature, complex molecular signaling pathways, defective cross talk between cells immune cells, hypoxic immunosuppressive effects microenvironment result treatment resistant metastatic phenotype. Over past years, immunotherapy has emerged as an attractive option against multiple malignancies. The unique ability natural killer (NK) to target cancer without antigen specificity makes them ideal candidate for use tumors. However, outcomes adoptive NK cell infusions into patients have been disappointing. Extensive studies done investigate different strategies improve function, trafficking targeting. Use cytokines cytokine analogs well described utilized enhance proliferation, stimulation persistence cells. Other techniques like blocking human leukocyte antigen-killer receptors (KIR) interactions anti-KIR monoclonal antibodies, preventing CD16 receptor shedding, increasing expression activating NKG2D, immunocytokines checkpoint inhibitors can mediated cytotoxicity. Using genetically modified chimeric bispecific trispecific engagers, be effectively redirected improving their cytotoxic potential. In this review, we these highlighted need further optimize clinical outcome based