# IL-2 Receptor Expression in Renal Cell Carcinoma Cells: IL-2 Influences Cell Survival and Induces Cell Death

## TL;DR

This study shows that interleukin-2 (IL-2) can directly affect kidney cancer cells by influencing their survival and death, suggesting a new potential treatment approach.

## Contribution

The study demonstrates for the first time that IL-2 directly impacts renal cell carcinoma cells through functional IL-2 receptors.

## Key findings

- IL-2 receptors (IL-2Rα, IL-2Rβ, IL-2Rγ) are expressed on the surface of four human RCC cell lines.
- rhIL-2 influences cell survival and death in a cell-line-dependent manner in RCC cells.
- Apoptotic markers like cleaved PARP and caspases are detected in RCC cells treated with rhIL-2.

## Abstract

Renal cell carcinoma (RCC) is the most common form of kidney cancer in adults. Immunotherapy, such as the application of interleukin-2 (IL-2), is a crucial treatment. It is known that IL-2 is involved in the upregulation of the anti-tumor immune response; however, a direct action of IL-2 on RCC cells has not yet been demonstrated. In this project, we aimed to investigate the expression and the functionality of the IL-2Rα, IL-2Rβ, and IL-2Rγ subunits on the four human RCC cell lines A-498, ACHN, Caki-1, and Caki-2. The expression of the three subunit genes was investigated via PCR, agarose gel of PCR products, Western blot, and flow cytometry. IL-2R functionality was assessed in RCC cells cultured with or without rhIL-2 using MTT and BrdU assays to investigate cell viability and proliferation; LDH assays, Live-or-Dye staining, and Annexin V/PI staining to study cell death; and Western blot to detect apoptotic markers, cleaved PARP, and cleaved caspases 3 and 9. Expression of IL-2Rα, IL-2Rβ, and IL-2Rγ subunits in the four cell lines was observed at the protein level with Western blot. Flow cytometry confirmed the cell-surface expression of IL-2Rα, IL-2Rβ, and IL-2Rγ subunits. In addition, we observed that rhIL-2 influenced cell survival/proliferation and cell death, depending on the cell line. We conclude that IL-2R is functional in RCC cells and that rhIL-2 could be used as a therapeutic option to act directly on RCC cells. However, further studies are required to elucidate the signaling pathways triggered by the IL-2-receptor binding on RCC cells.