RATIONALE: Evidence has shown that inhaled lung carcinogens, such as tobacco smoke, silica, or asbestos, induce a T-helper cell type 17 inflammatory environment. Interleukin-17A (commonly and hereafter called IL-17) is the signature cytokine of T-helper cell type 17 inflammation. We have shown previously that IL-17 overexpression promotes growth of lung adenocarcinoma in transgenic mouse models. Our additional findings suggest that IL-17 suppresses the function of the p53 tumor suppressor protein in a mutant K-Ras-expressing lung tumor cell line. OBJECTIVES: To compare our studies in mice to clinical samples. METHODS: We have used informatics and RNA sequencing-based approaches to analyze primary human lung adenocarcinoma samples. RESULTS: Comprehensive transcriptome analyses have shown that IL-17 expression positively correlates with expression of serine/arginine-rich splicing factor 1 (SRSF1), a key cellular splicing factor. This observation correlates with our previous finding that IL-17 regulates the activity of serine/argininerich splicing factor 1. In accord, there are significant differences in the global splicing activity between the IL-17+ and IL-17- lung adenocarcinomas, indicating that IL-17 may affect the selectivity of RNA splicing events by targeting serine/argininerich splicing factor 1. Further, Ingenuity pathway analyses (Qiagen) have identified activation of key pathways in IL-17+ relative to IL17- lung adenocarcinomas. In these analyses, IL-18 signaling appears central to IL-17+ lung adenocarcinomas, which display prominent signatures related to inflammation and evasion of antitumor immunity. CONCLUSIONS: Our RNA sequencing-based transcriptome analyses of lung adenocarcinomas have identified a cohort of patients that may be good candidates for immune therapy.
- T-helper cell type 17 inflammation
- lung adenocarcinoma
- lung inflammation