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Cancer Immunol Res. 2018 Jun;6(6):645-657. doi: 10.1158/2326-6066.CIR-17-0554. Epub 2018 Apr 13.

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

Author information

1
Department of Medicine, Baylor College of Medicine, Houston, Texas.
2
National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina.
3
Department of Surgery, Baylor College of Medicine, Houston, Texas.
4
The Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, Texas.
5
Division of Pulmonary and Critical Care, The University of Texas MD Anderson Cancer Center, Houston, Texas.
6
Center for Translational Research in Inflammatory Diseases, Michael E. DeBakey VA, Houston, Texas.
7
Departments of Pathology and Immunology, Baylor College of Medicine, Houston, Texas.
8
Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas.
9
Biology of Inflammation Center, Baylor College of Medicine, Houston, Texas.
10
Alkek Center for Metagenomics and Microbiome Research, Baylor College of Medicine, Houston, Texas.
11
Department of Medicine, Baylor College of Medicine, Houston, Texas. farrahk@bcm.edu dcorry@bcm.edu.

Abstract

Somatic mutations can promote malignant transformation of airway epithelial cells and induce inflammatory responses directed against resultant tumors. Tumor-infiltrating T lymphocytes (TIL) in early-stage non-small cell lung cancer (NSCLC) secrete distinct proinflammatory 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 with adjacent tumor-free tissue, whereas Th17 cells are decreased in tumor infiltrating locoregional 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. Cancer Immunol Res; 6(6); 645-57. ©2018 AACR.

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