Interplay Between Immune Checkpoint Modulators and the Epithelial-to-Mesenchymal Transition Axis in Clear Cell Renal...

Area of Science:

• Oncology
• Immunology
• Molecular Biology

Background:

• Clear cell renal cell carcinoma (ccRCC) has a poor prognosis despite immune checkpoint inhibitor (ICI) therapies.
• The roles of many immune checkpoints (ICs) and their connection to epithelial-to-mesenchymal transition (EMT) in ccRCC are not well understood.
• PD-1 and PD-L1 are well-studied, but other ICs require further investigation for their prognostic value.

Purpose of the Study:

• To investigate the interplay between 20 ICs and EMT markers in ccRCC.
• To assess the combined prognostic relevance of these markers in ccRCC patients.
• To identify potential novel prognostic markers and therapeutic targets in ccRCC.

Main Methods:

• Transcriptomic profiling of ccRCC tumors and normal kidney tissue.
• Integrated bioinformatic analyses including differential expression, correlation, and survival analyses.
• Validation using single-cell RNA sequencing, immunohistochemistry, and multiplex secretory IC assays.

Main Results:

• Dysregulation of ICs, notably LAG3 and NT5E, was observed in ccRCC tumors.
• Higher expression of LAG3 and NT5E correlated with poorer overall survival in ccRCC patients.
• The combination of ICs with EMT phenotype improved prognostic discrimination compared to individual markers.

Conclusions:

• An EMT-Immune Checkpoint (EMT-IC) axis was identified in ccRCC, impacting tumor biology and patient outcomes.
• LAG3 and NT5E emerge as potential prognostic markers and therapeutic targets in ccRCC.
• Further research into the EMT-IC axis could lead to improved ccRCC treatment strategies.