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Published on: June 15, 2016
Avelumab reduces STAT3 expression with effects on IL-17RA and CD15
Wojciech Kacper Szlasa1, Natalia Julia Sauer2, Jakub Karwacki3
1Department of Minimally Invasive and Robotic Urology, University Center of Excellence in Urology, Wroclaw Medical University, Poland.
Background:
Avelumab is a human antibody that targets the programmed cell death ligand-1 (PD-L1) protein in cancer cells. Novel anticancer therapies for renal cell carcinoma (RCC) consider cluster of differentiation 15 (CD15) and interleukin 17 receptor A (IL-17RA) as potential targets. Notably, the expression of PD-L1, CD15 and IL-17RA is dependent on signal transducer and activator of transcription 3 (STAT3).
Objectives:
The aim of the study was to investigate whether targeting PD-L1 with avelumab alters the expression levels of CD15 and IL-17RA, and to assess the STAT3-mediated regulation of CD15 and IL-17RA.
Material And Methods:
We applied immunocytochemistry (ICC) and confocal laser scanning (CLS) microscopy to assess the expression and localization of the immunotherapy targets in 3 renal cancer cell lines and 1 healthy renal cell line.
Results:
After treatment with 20 ng/mL avelumab, renal cancer cells showed a reduction in STAT3 expression. The expression of CD15 increased in cancer cells that exhibited a high level of IL-17RA, and the membrane signal of CD15 was reduced. In other renal cancer cell lines, the expression of CD15 decreased. Conversely, the level of IL-17RA changed only in healthy renal cells after treatment with avelumab, with no impact on renal cancer cells.
Conclusions:
Our study suggests that the targeting of PD-L1 with avelumab alters the expression of CD15 and IL-17RA, which play an important prognostic and therapeutic role in novel anticancer therapy.
Insights
Avelumab treatment reduced STAT3 expression in renal cancer cells, altering CD15 and IL-17RA levels. This suggests PD-L1 targeting impacts novel anticancer therapy targets.
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.
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