Munich, Germany (UroToday.com) Immunotherapy currently holds wide interest particularly for the treatment of renal cell carcinoma (RCC). Determining mechanism behind immune resistance is important. Rodler S and a group from Germany investigated one such immune mediator that may allow tumor growth. IL-22 is known to directly stimulate tumor cells in a several types of cancers. The group investigated the role of IL-22 and its receptor in renal cell carcinoma patients with respect to their cancer-specific, overall, and progression-free survival.
RNA-sequencing data on 413 RCC cases were obtained from the Human Cancer Genome Atlas (TCGA) and was analyzed by the cBioPortal software tool. Tumor IL-22 and IL-22 receptor expression was used to stratify patients to determine their effect on overall and progression-free survival using Kaplan-Meier method. Another independent cohort of 40 RCC patients were then obtained. The tumor specimen was stained for IL-22 and IL-22 receptor expression. Outcomes were then compared using Kaplan-Meier method. Finally, an array of 11 RCC cell lines were screened for IL-22 receptor expression and their behavior was characterized in the presence and absence of IL-22.
RNA-sequencing data from TCGA showed a significantly longer median overall survival for patients with lower expression of IL-22 and IL-22 receptor (46.1 vs 85.5 months, p = 0.003). In 40 RCC patient cohort, expression of IL-22 (p<0.001) and IL-22 receptor (p<0.005) was significantly associated with poor outcomes. IL-22 receptor was differentially expressed among human RCC cell lines in RT-PCR analysis. Administration of recombinant human IL-22 led to significant increase in tumor invasiveness and reduced cytotoxicity after 48 hours of hypoxia in several RCC cell lines. Cytotoxicity assessment in recombinant IL-22 RCC cell lines with targeted drugs such as sunitinib, sorafenib, carbozantinib, and everolimus showed resistance to these therapies and less cytoxicity.
The group concludes that the cytokine IL-22 contributes to proliferation of RCC cell lines and confers resistance against multiple targeted agents. The expression of IL-22 receptor on RCC cells is associated with poor prognosis in two independent RCC cohorts (one from TCGA and another smaller cohort). IL-22 receptor may be used as a prognostic marker in RCC.
Reported By:
Mohammed Haseebuddin, MD, at the 31st Annual EAU Congress - March 12 - 15, 2016 – Munich, Germany
Fox Chase Cancer Center