Abstract
Lung cancer is the leading cause of cancer deaths worldwide. The cytokine interleukin-17A supports tumour vascularization and growth, however, its role in lung cancer is unknown. Here we show, in the lungs of patients with lung adenocarcinoma, an increase in interleukin-17A that is inversely correlated with the expression of T-bet and correlated with the T regulatory cell transcription factor Foxp3. Local targeting of interleukin-17A in experimental lung adenocarcinoma results in a reduction in tumour load, local expansion of interferon-γ-producing CD4(+) T cells and a reduction in lung CD4(+)CD25(+)Foxp3(+) regulatory T cells. T-bet((-/-)) mice have a significantly higher tumour load compared with wild-type mice. This is associated with the local upregulation of interleukin-23 and induction of interleukin-17A/interleukin-17R-expressing T cells infiltrating the tumour. Local anti-interleukin-17A antibody treatment partially improves the survival of T-bet((-/-)) mice. These results suggest that local anti-interleukin-17A antibody therapy could be considered for the treatment of lung tumours.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Adenocarcinoma / drug therapy
-
Adenocarcinoma / genetics
-
Adenocarcinoma / immunology*
-
Adenocarcinoma / metabolism
-
Adenocarcinoma / pathology
-
Adenocarcinoma of Lung
-
Administration, Intranasal
-
Adult
-
Aged
-
Animals
-
Antibodies, Neutralizing / administration & dosage
-
Antibodies, Neutralizing / therapeutic use*
-
Antigens, CD / immunology
-
Female
-
Forkhead Transcription Factors / genetics
-
Forkhead Transcription Factors / immunology*
-
Forkhead Transcription Factors / metabolism
-
Gene Expression Regulation, Neoplastic / drug effects
-
Gene Expression Regulation, Neoplastic / immunology*
-
Humans
-
Immunologic Surveillance
-
Interferon-gamma / biosynthesis
-
Interferon-gamma / immunology
-
Interleukin-17 / immunology
-
Interleukin-17 / metabolism
-
Interleukin-23 / immunology
-
Interleukin-23 / metabolism
-
Lung / drug effects
-
Lung / immunology*
-
Lung / metabolism
-
Lung / pathology
-
Lung Neoplasms / drug therapy
-
Lung Neoplasms / genetics
-
Lung Neoplasms / immunology*
-
Lung Neoplasms / metabolism
-
Lung Neoplasms / pathology
-
Male
-
Mice
-
Mice, Inbred C57BL
-
Mice, Knockout
-
Middle Aged
-
T-Box Domain Proteins / deficiency
-
T-Box Domain Proteins / genetics*
-
T-Box Domain Proteins / immunology
-
T-Lymphocytes, Regulatory / immunology
Substances
-
Antibodies, Neutralizing
-
Antigens, CD
-
Forkhead Transcription Factors
-
Foxp3 protein, mouse
-
Interleukin-17
-
Interleukin-23
-
T-Box Domain Proteins
-
T-box transcription factor TBX21
-
Interferon-gamma