Targeting Reactive Species Stress and Nutrient Sensing to Enhance NK-Cell Function: Mechanistic Strategies for Overcoming Pancreatic Cancer Progression and Resistance Through Supplement Therapy

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive disease with limited treatment success and strong resistance to therapy. Natural killer (NK) cells are important immune cells that can destroy cancer cells, and their function can be improved through certain micronutrients and dietary supplements. This review explores a "triple NK cell boost" strategy—enhancing NK cell frequency, cancer-killing ability, and ability to reach tumors—using antioxidants and food-derived supplements. These compounds may help reduce the harmful effects of reactive species which can weaken the immune system and support cancer growth. Additionally, we examine the emerging role of nutrient stress and metabolic sensing pathways in shaping NK cell suppression in PDAC. By modulating both redox and nutrient stress responses mechanisms, supplement therapy may help overcome immune evasion and drug resistance in PDAC, offering a promising direction for better prevention and treatment.