IL17A Regulates Tumor Latency and Metastasis in Lung Adeno and Squamous SQ.2b and AD.1 Cancer.

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IL17A Regulates Tumor Latency and Metastasis in Lung Adeno and Squamous SQ.2b and AD.1 Cancer.

Cancer Immunol Res. 2018 Apr 13;:

Authors: You R, DeMayo FJ, Liu J, Cho SN, Burt BM, Creighton CJ, Casal RF, Lazarus DR, Lu W, Tung HY, Yuan X, Hill AA, Kim M, Perusich S, Cornwell LD, Rosen D, Song LZ, Paust S, Diehl GE, Corry DB, Kheradmand F

Abstract
Somatic mutations can promote malignant transformation of airway epithelial cells, and induce inflammatory responses directed against resultant tumors. Tumor-infiltrating T lymphocytes (TILs) in early stage non-small cell lung cancer (NSCLC) secrete distinct pro-inflammatory cytokines, but the contribution of these TILs to tumor development and metastasis remains unknown. We show here that TILs in early stage NSCLC are biased toward IL17A expression (Th17) when compared to adjacent tumor-free tissue, whereas Th17 cells are decreased in tumor infiltrating loco-regional lymph nodes in advanced NSCLC. Mice in which Pten and Smad4 (Pts4d/d) are deleted from airway epithelial cells develop spontaneous tumors, that share genetic signatures with squamous- (SQ.2b), and adeno- (AD.1) subtypes of human NSCLC. Pts4d/d mice globally lacking in IL17a (Pts4d/dIl17a-/-) showed decreased tumor latency and increased metastasis. Th17 cells were required for recruitment of CD103+ dendritic cells, and adoptive transfer of IL17a-sufficient CD4+ T cells reversed early tumor development and metastasis in Pts4d/dIl17a-/- mice. Together, these findings support a key role for Th17 cells in TILs associated with the Pts4d/d model of NSCLC and suggest therapeutic and biomarker strategies for human SQ2b and AD1 lung cancer.

PMID: 29653981 [PubMed - as supplied by publisher]

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