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T helper 17 cells play a critical pathogenic role in lung cancer.

Authors
  • Chang, Seon Hee
  • Mirabolfathinejad, Seyedeh Golsar
  • Katta, Harshadadevi
  • Cumpian, Amber M
  • Gong, Lei
  • Caetano, Mauricio S
  • Moghaddam, Seyed Javad
  • Dong, Chen
Type
Published Article
Journal
Proceedings of the National Academy of Sciences
Publisher
Proceedings of the National Academy of Sciences
Publication Date
Apr 15, 2014
Volume
111
Issue
15
Pages
5664–5669
Identifiers
DOI: 10.1073/pnas.1319051111
PMID: 24706787
Source
Medline
Keywords
License
Unknown

Abstract

Lung cancer development is associated with extensive pulmonary inflammation. In addition, the linkage between chronic obstructive pulmonary disease (COPD) and lung cancer has been demonstrated in population-based studies. IL-17-producing CD4 helper T cells (Th17 cells) play a critical role in promoting chronic tissue inflammation. Although Th17 cells are found in human COPD and lung cancer, their role is not understood. We have thus used a mouse model of lung cancer, in which an oncogenic form of K-ras (K-ras(G12D)), frequently found in human lung cancer, is restrictedly expressed in lung epithelial cells [via Clara cell secretory protein (CCSP(cre))]. In this model, Th17 and Treg but not Th1 cells were found enriched at the tumor tissues. When CCSP(cre)/K-ras(G12D) mice were weekly challenged with a lysate of nontypeable Haemophilus influenza (NTHi), which induces COPD-type inflammation and accelerates the tumor growth, they showed greatly enhanced Th17 cell infiltration in the lung tissues. Lack of IL-17, but not IL-17F, resulted in a significant reduction in lung tumor numbers in CCSP(cre)/K-ras(G12D) mice and also those treated with NTHi. Absence of IL-17 not only resulted in reduction of tumor cell proliferation and angiogenesis, but also decreased the expression of proinflammatory mediators and reduced recruitment of myeloid cells. Depletion of Gr-1(+)CD11b(+) myeloid cells in CCSP(cre)/K-ras(G12D) mice suppressed tumor growth in lung, indicating Gr-1(+)CD11b(+) myeloid cells recruited by IL-17 play a protumor role. Taken together, our data demonstrate a critical role for Th17 cell-mediated inflammation in lung tumorigenesis and suggest a novel way for prevention and treatment of this disease.

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