Immune self-tuning in renal cell carcinoma patients

Abstract

e22069 Background: Renal cell carcinoma (RCC) cells can inhibit protective antitumor immunity by secretion of immunosuppressive factors leading to the induction of regulatory T cells. The objective of this study was to investigate the prognostic impact of mRNA expression levels of IL10, TGFβ and forkhead box transcription factor (FoxP3) mRNA in peripheral blood mononuclear cells (PBMCs) of metastatic RCC patients before receiving treatment with sorafenib. Methods: PBMCs of 46 patients were assessed for their expression levels of TGFβ, IL10 and FoxP3 by quantitative RT-PCR. Clinical features considered included ECOG performance status, hemoglobin, alkaline phosphatase, and calcium concentrations. Disease evaluation was performed every 8 weeks following RECIST criteria. Relationship between pre-treatment factors and survival were examined in univariate analyses and subsequently by multivariate analysis using a stepwise Cox regression model. Results: In contrast to FoxP3, mRNA expression levels of IL10 and TGFβ were significantly higher in the 46 RCC patients compared to healthy volunteers: Median expression levels [ratio marker /housekeeping gene PBGD] were 5.56E-05 vs 2.05E-04 (P=0.034) for IL10 and 7.38E-02 vs 3.04E- 01 (P=0.023) for TGFβ. Univariate analysis revealed a negative prognostic influence of IL10 on progression free survival (p=0.04) and on overall survival, although not significant (P= 0.063). Surprisingly, high TGFβ and FoxP3 expression levels had a positive influence on progression free (P<0.001 and P=0.047, respectively) and overall survival (P<0.001 and P= 0.031, respectively). In the multivariate analysis low ECOG performance status and high TGFβ mRNA expression levels were independently associated with worse progression free (P=0.001 and P=0.054,) and worse overall survival (P=0. 006 and P< 0.001, respectively). Conclusions: RCC caused an immune-suppressive phenotype in PBMC characterized by increased mRNA expression levels of IL10 and TGFβ. Surprisingly, in contrast to IL10, a high TGFβ mRNA expression level was an independent good prognostic factor. Whether this observation can be attributed to recently described immune promoting functions of TGFβ needs to be determined. No significant financial relationships to disclose.