A combined intervention of aerobic training and pineapple extract attenuates PD-1 expression in the melanoma tumor microenvironment, independent of systemic IL-10

This study aimed to evaluate the individual and combined effects of aerobic training (AT) and pineapple supplementation (extract) on programmed cell death protein 1 (PD-1) gene expression within the tumor microenvironment and on systemic interleukin-10 (IL-10) levels in a murine melanoma model. Twenty C57BL/6 mice were randomly assigned into four groups (n=5 per group) following melanoma tumor induction: Tumor control, AT, Pineapple Supplement (PS), and AT+PS. The AT group underwent a structured aerobic training program, while the PS group received pineapple extract (300 mg/kg/day) via oral gavage for six weeks. Serum IL-10 concentrations were quantified by ELISA, and PD-1 mRNA expression in tumor tissue was analyzed using quantitative RT-PCR. All intervention groups—AT, PS, and their combination—resulted in a significant downregulation of PD-1 gene expression within the tumor compared to the control group (p < 0.05). In contrast, neither AT nor PS alone significantly altered systemic IL-10 levels. The combination therapy (AT+PS) produced the most pronounced suppression of PD-1 and was the only intervention to elicit a significant, though modest, reduction in serum IL-10. These findings indicate that the primary immunomodulatory effect of these interventions is localized to the tumor microenvironment and is largely independent of systemic IL-10 signaling. The synergistic combination of aerobic training and pineapple supplementation potently suppresses PD-1 gene expression, suggesting a promising, non-pharmacological strategy for enhancing anti-tumor immunity. Further investigation is required to confirm these effects at the protein level and to elucidate the underlying mechanisms.