Determining the Impact of NK Cells on Each Stage of Cancer Progression

Abstract

Natural Killer (NK) cells are crucial regulators of anti-tumor immunity, but their activity is importantly shaped by the tumor microenvironment across diverse cancer types. This study investigates how variations in cytokine and chemokine presence, ROS dynamics, and effector-to-target (E:T) ratios influence NK cell phenotype and cytotoxic function in Lung, Breast, Ovarian, Gastric, Renal, Colon & Colorectal cancers. Using experimental killing essays and patient data, this paper demonstrates that higher E:T ratios and a predominance of mature NK cells are closely linked to increased cancer cell death. This data also suggests that anti-inflammatory cytokines (IL-12, IFN-γ) enhance NK cell function while immunosuppressive cytokines (IL-10, IL-6) and elevated ROS levels suppress cytotoxicity. Single-cell and pathway data highlight how the balance of these molecules vary across tumor microenvironments. The findings support the development of NK cell based therapies aimed at restoring cytotoxicity and anti-tumor immunity, providing insight into the interplay between cytokines, ROS, and NK cell activity.