Avelumab reduces STAT3 expression with effects on IL-17RA and CD15

Area of Science:

• Immunology
• Oncology
• Cell Biology

Background:

• Avelumab targets programmed cell death ligand-1 (PD-L1) on cancer cells.
• Cluster of differentiation 15 (CD15) and interleukin 17 receptor A (IL-17RA) are novel targets for renal cell carcinoma (RCC) therapy.
• Signal transducer and activator of transcription 3 (STAT3) regulates PD-L1, CD15, and IL-17RA expression.

Purpose of the Study:

• To investigate if avelumab targeting PD-L1 affects CD15 and IL-17RA expression.
• To assess STAT3-mediated regulation of CD15 and IL-17RA in renal cancer.

Main Methods:

• Immunocytochemistry (ICC) and confocal laser scanning (CLS) microscopy were used.
• Expression and localization of targets were assessed in three RCC cell lines and one healthy renal cell line.
• Cells were treated with 20 ng/mL avelumab.

Main Results:

• Avelumab treatment reduced STAT3 expression in renal cancer cells.
• CD15 expression increased in cancer cells with high IL-17RA, while membrane CD15 signal decreased.
• CD15 expression decreased in other renal cancer cell lines; IL-17RA levels were unaffected in cancer cells but changed in healthy cells.

Conclusions:

• Targeting PD-L1 with avelumab alters CD15 and IL-17RA expression.
• CD15 and IL-17RA have prognostic and therapeutic roles in novel anticancer therapies.
• STAT3 signaling is implicated in the regulation of these targets.