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<p>Melanoma is an aggressive skin cancer that thrives within an immunosuppressive tumor microenvironment. This study evaluated the effects of istradefylline (IST), vitamin D (VTD), and their combination on tumor progression and immunobiochemical parameters in B16F10 melanoma-bearing mice. Male C57BL/6 mice were inoculated subcutaneously with B16F10 melanoma cells (2 × 10<sup>5</sup> cells/animal) and monitored for 15&#xa0;days to establish tumors. Mice with tumor volumes of approximately 100 mm<sup>3</sup> were divided into five groups: Control (CTR), melanoma-bearing (MEL), MEL + IST (1&#xa0;mg/kg body weight), MEL + VTD (1000&#xa0;IU/kg body weight), and MEL + IST + VTD. Treatments were administered orally for 14&#xa0;days, after which the animals were euthanized and spleen lymphocytes were collected for biochemical analysis. Untreated MEL mice exhibited significantly increased tumor volume, elevated ecto-nucleoside triphosphate diphosphohydrolase (E-NTPDase) activity, and reduced adenosine deaminase (ADA) activity compared with CTR and treated groups. Additionally, MEL mice showed higher arginase and myeloperoxidase activities, reduced nitric oxide (NOx) levels, increased malondialdehyde (MDA) content, and dysregulated cytokine profiles. Treatment with IST and VTD, particularly their combination, reduced tumor growth and ameliorated immunosuppressive and oxidative stress markers. These findings indicate that adenosine A₂A receptor blockade by IST, in combination with vitamin D’s immunomodulatory effects, may enhance antitumor immunity and mitigate melanoma progression.</p>

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Effect of istradefylline, vitamin D, and their combination on tumor growth and immunosuppressive biomarkers in B16F10 tumor-bearing mice

  • 期刊论文

  • 发表日期：

    2026年3月24日

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  • Odunayo Michael Agunloye,
  • Renan da Silva Ebone,
  • Pedro Henrique Doleski,
  • Thayanara Cruz da Silva,
  • Jean Lucas Gutknecht da Silva,
  • Mayara da Rosa Sagrilo,
  • Viviane do Carmo Goncalves Souza,
  • Rafaella Pereira da Silveira,
  • William Douglas dos Santos,
  • Pietra do Santos de Oliveira,
  • Daniela B. R. Leal

摘要

Melanoma is an aggressive skin cancer that thrives within an immunosuppressive tumor microenvironment. This study evaluated the effects of istradefylline (IST), vitamin D (VTD), and their combination on tumor progression and immunobiochemical parameters in B16F10 melanoma-bearing mice. Male C57BL/6 mice were inoculated subcutaneously with B16F10 melanoma cells (2 × 105 cells/animal) and monitored for 15 days to establish tumors. Mice with tumor volumes of approximately 100 mm3 were divided into five groups: Control (CTR), melanoma-bearing (MEL), MEL + IST (1 mg/kg body weight), MEL + VTD (1000 IU/kg body weight), and MEL + IST + VTD. Treatments were administered orally for 14 days, after which the animals were euthanized and spleen lymphocytes were collected for biochemical analysis. Untreated MEL mice exhibited significantly increased tumor volume, elevated ecto-nucleoside triphosphate diphosphohydrolase (E-NTPDase) activity, and reduced adenosine deaminase (ADA) activity compared with CTR and treated groups. Additionally, MEL mice showed higher arginase and myeloperoxidase activities, reduced nitric oxide (NOx) levels, increased malondialdehyde (MDA) content, and dysregulated cytokine profiles. Treatment with IST and VTD, particularly their combination, reduced tumor growth and ameliorated immunosuppressive and oxidative stress markers. These findings indicate that adenosine A₂A receptor blockade by IST, in combination with vitamin D’s immunomodulatory effects, may enhance antitumor immunity and mitigate melanoma progression.