Serum levels of the IL-6 family of cytokines predict prognosis in renal cell carcinoma (RCC)

Abstract

Purpose An improved understanding of RCC immunology should shed further light on RCC tumor biology. Our objective was to study to what extent serum levels of the IL-6 family of cytokines at diagnosis were relevant to survival. Methods A total of 118 consecutively patients with RCC, in which the tumor was surgically removed at Haukeland University Hospital during the period from 2007 to 2010, were included. The patients were followed-up for 10 years. The morning before surgery blood was sampled and serum frozen, with levels of IL-6, IL-27, IL-31, OSM, CNTF, IL-6Rα and gp130 determined. Results Among patients with the highest quartile of IL-6 (> 8 pg/ml) ( n = 29), six of nine who had metastasis at diagnosis had such high IL-6 values. Among presumed radically treated patients, a high IL-6 and IL-27 strongly predicted recurrence. In particular, the predictions among patients with large (diameter > 7 cm) tumors were excellent regarding both IL-6 and IL-27 values. High gp130 serum levels predicted an overall survival (OS) among RCC patients with large tumors. Patients with a high IL-6 exhibited a strong expression of IL-6 in endothelial- and vascular smooth muscle cells. Moreover, the level of intra-tumoral CD3-positive cells predicted survival. Conclusions IL-6 and IL-27 seem to play a role in RCC biology. IL-6 enables the pinpointing of metastatic condition at diagnosis, as well as together with IL-27, the predicting of survival and recurrence. Endothelial cells and vascular smooth muscle cells are both suggested as important sources of IL-6. Electronic supplementary material The online version of this article (10.1007/s00262-020-02655-z) contains supplementary material, which is available to authorized users.

Increased systemic IL-6 levels point to inflammation as a determinant of renal cell carcinoma development

“…In this study, only IL-6 was present at significantly higher levels in renal cancer patients compared to controls. This result adds to the growing evidence of the role of IL-6 in the development and progression of renal cancer 6,27 . IL-6 promotes cell proliferation, migration, and invasion mainly by the activation of transcription factors STAT3 and NF-κB [28][29][30][31] .…”

Tumor-Induced Inflammatory Cytokines and the Emerging Diagnostic Devices for Cancer Detection and Prognosis

“…Dysregulation in circulating cytokine levels has been correlated with the presence of many types of cancers, the severity of cancer as well as the effectiveness of a certain therapy thus may serve as quality biomarkers to support diagnosis and prognosis ( Figure 2 ). For example in renal cell carcinoma, a high IL-6 correlates to cancer metastasis, while high IL-6 and IL-17 measurements predict cancer recurrence following radical treatment ( 98 ). Other recent examples of the use of circulating systemic protein for prognosis are serum CRP levels, in which high levels are associated with poor survival in patients with gastric cancer based on a meta-analysis, independent of country of origin, cancer stage, and study design ( 99 ), and serum CCL-2 levels, in which high levels are associated with poor prognosis and survival of patients with pancreatic cancer, independent of gender, age and the stage of cancer ( 100 ).…”

Single‐cell analysis reveals metastatic cell heterogeneity in clear cell renal cell carcinoma

“…These differences reflect well-known disparities in clonal selection following cell evolution in tumour metastasis. 35…”