Abstract
BackgroundRenal cell carcinoma (RCC) is a tumor with immunogenic properties. Soluble interleukin-2 receptor (sIL-2R) has a role in T cell activation and may be important for immune regulation in various conditions, including infections, transplantation rejection, autoimmune inflammatory states, and cancer. We investigated the prognostic value of the serum sIL-2R level in patients with metastatic RCC receiving IFN-alpha and vascular endothelial growth factor (VEGF)-targeting therapy.MethodsWe monitored the serum level of sIL-2R over time and examined phosphorylated Akt expression by the primary tumor in 47 patients with metastatic clear cell RCC (ccRCC) undergoing cytoreductive nephrectomy followed by first-line adjuvant therapy with IFN-alpha plus sequential VEGF-targeting therapy as second- or third-line adjuvant therapy.ResultsA preoperative increase of the serum level of sIL-2R was correlated with a higher preoperative serum level of programmed cell death 1 (PD-1)-ligand 1 (PD-L1), increased expression of phosphorylated Akt by the primary tumor, and a worse response to IFN-alpha/sequential VEGF-targeting therapy, as well as being an independent prognostic factor for a shorter overall survival time by multivariate analysis. Over time, the serum sIL-2R level largely reflected the tumor response to therapy.ConclusionsMonitoring the serum level of sIL-2R may help to predict the biological behavior of ccRCC, its response to IFN-alpha/sequential VEGF-targeting therapy, and the prognosis.
Highlights
Renal cell carcinoma (RCC) is a tumor with immunogenic properties
An increase of the preoperative Soluble interleukin-2 receptor (sIL-2R) level was detected in patients with poorly differentiated cancer (Fuhrman grade 1/2; mean ± S.D. = 322.9 ± 264.6, Fuhrman grade 3/ 4; 778.8 ± 594.5, P = 0.002), local invasion, lymph node metastasis, and vascular invasion
We found that the serum sIL-2R level remained nearly constant when RCC showed a good response to IFN-alpha with sequential vascular endothelial growth factor (VEGF)-targeting therapy, while sIL-2R began to increase when resistance to therapy developed, indicating that monitoring serum sIL-2R may help to assessing tumor activity
Summary
Renal cell carcinoma (RCC) is a tumor with immunogenic properties. Soluble interleukin-2 receptor (sIL-2R) has a role in T cell activation and may be important for immune regulation in various conditions, including infections, transplantation rejection, autoimmune inflammatory states, and cancer. IL-2R alpha is released by T cells as a soluble form (soluble interleukin-2 receptor: sIL-2R), and elevation of the sIL-2R level is detected in patients with infectious diseases, transplantation rejection, autoimmune inflammation, and cancer [9,10,11]. It seems that sIL-2R release promotes T cell activation and is important for immune regulation in various conditions
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