Abstract
IL-7/IL-7 receptor (IL-7R) interactions have been shown to prevent apoptosis in lung cancer cells and promote stromal pro-tumor immune cell homing and differentiation. The aim of this study is to investigate the correlation between tumoral IL-7R expression and stromal pro-tumor immune cells (FoxP3+ Tregs and CD163+ M2 macrophages) and to determine prognostic impact of the combination of these markers in lung adenocarcinomas. In resected stage I lung adenocarcinoma (n=913; 1995-2009), antigen expression of IL-7R, FoxP3 and CD163 was evaluated by immunohistochemistry (IHC) using tissue microarrays and mRNA expression was quantified by RT-PCR. Prognosis was analyzed by both recurrence free probability (RFP) and lung cancer-specific survival (LCSS). In IHC analysis, high tumoral IL-7R, stromal FoxP3, and stromal CD163 expression were individually associated with lymphatic/vascular invasion, and increasing percentage of solid histological patten. A correlation was seen between IL-7R, FoxP3 and CD163 expression by mRNA and IHC analyses (Figure1). The co-existence of high expression of these 3 markers was found in 16% of patients and was associated with worse outcomes (Figure2). In multivariable analysis, triple marker co-existence was an independent risk factor for RFP (p=0.004) and LCSS (p=0.008). Tumoral IL-7 receptor is a potential target for lung adenocarcinoma immunotherapy.View Large Image Figure ViewerDownload Hi-res image Download (PPT)
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