T-Cell Receptor Repertoire as a Predictor of Immune-Related Adverse Events in Renal Cell Carcinoma

• Published in: Current issues in molecular biology 2023-11, Vol.45 (11), p.8939-8949
• Main Authors: Kobayashi, Takuro, Nagata, Masayoshi, Ikehata, Yoshihiro, Nagashima, Yuki, Nagaya, Naoya, Lu, Yan, Horie, Shigeo
• Format: Article
• Language: English
• Subjects: immune checkpoint inhibitors; ipilimumab; nivolumab; renal cell carcinoma; repertoire analysis
• ISSN: 1467-3045; 1467-3037; 1467-3045
• DOI: 10.3390/cimb45110561

Immune checkpoint inhibitors (ICIs) are effective in treating renal cell carcinoma (RCC) but can also cause immune-related adverse events (irAEs). The relationship between irAEs and the T-cell receptor (TCR) repertoire in RCC patients treated with ICIs remains unclear. We analyzed the relationship between the severity and diversity of irAEs and the TCR repertoire in RCC patients who received dual checkpoint inhibitors (ipilimumab + nivolumab). The TCRβ (TRB) repertoires were characterized in peripheral blood samples from six patients with RCC before the initiation of ICI therapy. The diversity and clonality of the TCR repertoire were compared between patients with grade 2 and grade 3 irAEs. The median proportion of top 10 unique reads in the TCR repertoire was significantly higher in grade 3 compared with grade 2 irAEs in RCC patients receiving immune checkpoint inhibitors (grade 2: 0.196%; grade 3: 0.346%; p = 0.0038). We provide insight into the relationship between TCR repertoire and irAEs in RCC patients treated with ICIs. TCR repertoire clonality may be associated with the development of irAEs in RCC patients.