Role of Nivolumab in the Modulation of PD-1 and PD-L1 Expression in Papillary and Clear Cell Renal Carcinoma (RCC)

Area of Science:

• Oncology
• Immunology
• Cell Biology

Background:

• The expression and mechanisms of programmed cell death-1 (PD-1) and its ligands (PD-L1, PD-L2) in renal cancer are not fully understood.
• Immune checkpoint inhibitors like nivolumab offer therapeutic potential but require deeper mechanistic insight for different renal carcinoma subtypes.

Purpose of the Study:

• To investigate the response of clear cell (cc)RCC and papillary (p)RCC subtypes to nivolumab.
• To analyze the impact of nivolumab on PD-1/PD-L1 expression and associated signaling pathways in renal carcinoma cells.

Main Methods:

• Analysis of PD-1 and PD-L1 expression in ccRCC and pRCC cell lines.
• Treatment of cell lines with varying doses of nivolumab.
• Assessment of cellular behavior (aggressiveness, spheroid formation) and signaling pathway activity (AKT, S6, androgen receptors).

Main Results:

• All analyzed renal carcinoma cell lines expressed PD-1; ccRCC and one pRCC line expressed PD-L1.
• Nivolumab increased PD-1 levels and differentially affected cell behavior: diminishing aggressiveness in ccRCC but increasing it in pRCC.
• Nivolumab modulated AKT activity differently across subtypes and increased androgen receptor expression in a nivolumab-dependent spheroid-forming pRCC line.

Conclusions:

• Renal carcinoma subtypes exhibit complex and distinct responses to nivolumab treatment.
• pRCC cells showed increased tumorigenicity and PD-1/PD-L1 levels, whereas ccRCC showed diminished tumorigenicity.
• Further research into subtype-specific molecular pathways is crucial for optimizing nivolumab-based therapies for renal carcinoma.