Baseline IFN-γ-based natural killer cell activity is associated with ex vivo expansion capacity of autologous NK cells in patients with breast cancer

Abstract Background Natural killer (NK) cell-based immunotherapy is increasingly explored in cancer treatment; however, inter-individual variability in NK cell expansion remains a major challenge. Clinically applicable biomarkers reflecting NK cell functional fitness prior to expansion are limited. Methods Peripheral blood samples from 33 patients with breast cancer were analyzed using a standardized whole-blood interferon-gamma (IFN-γ) release assay to assess baseline NK cell activity. NK cells were subsequently expanded ex vivo from peripheral blood mononuclear cells under cytokine-based culture conditions. Associations were evaluated using Spearman’s rank correlation. Results Baseline NK cell activity showed a significant positive correlation with NK cell expansion capacity ( r = 0.46, p = 0.007). In contrast, age, leukocyte counts, peripheral NK cell frequency, and initial NK cell number were not significantly associated with expansion outcomes. Conclusions Baseline IFN-γ-based NK cell activity is associated with the ex vivo expansion capacity of autologous NK cells and may serve as a candidate biomarker for predicting ex vivo NK-cell expansion and warrants validation in larger studies for optimizing NK cell-based immunotherapy strategies in patients with breast cancer.