Journal
CANCER IMMUNOLOGY RESEARCH
Volume 6, Issue 6, Pages 645-657Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/2326-6066.CIR-17-0554
Keywords
-
Categories
Funding
- VA Merit Awards [R01HL117181-01, CX000104, BX002221]
- Cytometry and Cell Sorting Core at Baylor College of Medicine
- NIH [AI036211, CA125123, RR024574, UM1HG006348]
- Cancer Prevention and Research Institute of Texas [RP120713]
- NATIONAL CANCER INSTITUTE [P30CA125123] Funding Source: NIH RePORTER
- NATIONAL HUMAN GENOME RESEARCH INSTITUTE [UM1HG006348] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R01AI125264] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES [ZIAES103311] Funding Source: NIH RePORTER
- Veterans Affairs [I01CX000104] Funding Source: NIH RePORTER
Ask authors/readers for more resources
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 (Pts4(d/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. Pts4(d/d) mice globally lacking in IL17a (Pts4(d/d)Il17a(-/-)) 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 Pts4(d/d)Il17a(-/-) mice. Together, these findings support a key role for Th17 cells in TILs associated with the Pts4(d/d) model of NSCLC and suggest therapeutic and biomarker strategies for human SQ2b and AD1 lung cancer. (C) 2018 AACR.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available