Journal of Exercise & Organ Cross Talk
Journal of Eexercise & Organ Cross Talk

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

Document Type : Original Article

Authors

Maryam Movasagh
Hossein Abednatanzi
Mandana Gholami
Farshad Ghazalian

Department of physical education and sport sciences, SR.C., Islamic Azad university, Tehran, Iran.

https://doi.org/10.22122/jeoct.2025.548717.1173
Abstract
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.

What is already known on this subject?

Therapeutic inhibition of PD-1 has transformed melanoma treatment by rejuvenating exhausted T cells and inducing durable anti-tumor immunity.

 

What this study adds?

The combined intervention also significantly lowers systemic IL-10 levels, suggesting a complex immunomodulatory effect.

Keywords

Tumor microenvironment
Cancer immunotherapy
PD-1/PD-L1 axis
Interleukin-10
Ananas comosus (Pineapple) supplementation
Aerobic exercise
Melanoma model

Subjects

Acknowledgements

None

Funding

None

Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Compliance with ethical standards

Conflict of interest The authors declare that there is no conflict of interest in the present research.

Ethical approval This study received approval under the research ethics code IR.SSRC.REC.1401.342 from the Azad University of Sciences and Research.

Informed consent Animal study. 

Author contributions 

Conceptualization: M.M., H.A, F.Gh., M.GH., Methodology: M.M., H.A, F.Gh., M.GH., Software: M.M., H.A, F.Gh., M.GH., Validation: M.M., H.A, F.Gh., M.GH.,; Formal analysis: M.M., H.A, F.Gh., M.GH.,; Investigation: M.M., H.A, F.Gh., M.GH.,; Resources: M.M., H.A, F.Gh., M.GH.,; Data curation: M.M., H.A, F.Gh., M.GH.,; Writing - original draft: M.M., H.A, F.Gh., M.GH.,; Writing–review & editing: M.M., H.A, F.Gh., M.GH.,; Visualization: M.M., H.A, F.Gh., M.GH.,; Supervision: H.A.; Project administration: H.A.,.; Funding acquisition: H.A.   

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Journal of Exercise & Organ Cross Talk
Volume 5, Issue 3
Summer 2025
Pages 123-129

  • Receive Date 22 July 2025
  • Revise Date 07 September 2025
  • Accept Date 12 September 2025

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