INFLUENCE OF KCNN4 ON IMMUNE RESPONSE IN ATHLETES: MODULATION OF TUMOR SUPPRESSION IN RENAL CELL CARCINOMA THROUGH REGULATORY T CELLS AND RESTING MAST CELLS

Authors

  • Yi Xiaoming Department of Urology, Jingling College of Clinical Medicine, Nanjing Medical University, Nanjing 210002, China.
  • Fu Dian Department of Urology, Jingling College of Clinical Medicine, Nanjing Medical University, Nanjing 210002, China.
  • Zhou Yulin Department of Urology, Jingling College of Clinical Medicine, Nanjing Medical University, Nanjing 210002, China.
  • Cui Yankang Department of Urology, Jingling College of Clinical Medicine, Nanjing Medical University, Nanjing 210002, China.
  • He Haowei Department of Urology, Jingling College of Clinical Medicine, Nanjing Medical University, Nanjing 210002, China.
  • Tang Chaopeng Department of Urology, Jingling College of Clinical Medicine, Nanjing Medical University, Nanjing 210002, China.
  • Xia Chen Department of Infectious Diseases, Children’s Hospital of Nanjing Medical University, Nanjing 210000, China.
  • Cheng Wen Department of Urology, Jingling College of Clinical Medicine, Nanjing Medical University, Nanjing 210002, China.
  • Zhou Wenquan Department of Urology, Jingling College of Clinical Medicine, Nanjing Medical University, Nanjing 210002, China.

Keywords:

Clear cell renal cell carcinoma；KCNN4；Tregs；Resting mast cells；Immune response

Abstract

Objective: To explore the regulatory role of the KCNN4 gene in athletes diagnosed with renal clear cell carcinoma (RCC) and its impact on immune response mechanisms. Methods: Utilized datasets from the GSE53757 and TCGA to analyze the expression of KCNN4 in RCC tissues, examining its correlation with T cell regulatory (Treg) markers and resting mast cells via flow cytometry, qPCR, and immunohistochemistry. Investigated the effects of modifying KCNN4 expression on Treg activity and resting mast cell levels in RCC cells, using inhibitors and interference plasmids. Results: Data showed elevated KCNN4 expression in RCC tissues, correlating positively with Treg proliferation and negatively with resting mast cell activity. Functional assays revealed enhanced Treg suppressive factors and reduced pro-inflammatory markers in cells with upregulated KCNN4. Conversely, downregulation of KCNN4 led to decreased Treg activity and increased mast cell response, enhancing anti-tumor immunity. Conclusion: KCNN4 plays a crucial role in modulating the immune environment in athletes with RCC by influencing Treg and mast cell functions, suggesting potential therapeutic targets for enhancing anti-tumor responses in this population.

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Published

2024-02-01

Issue

Vol. 24 No. 95 (2024): Vol. 24, No. 95, marzo/March 2024

Section

Manuscript