Cigarette smoke impairs NK cell-dependent tumor immune surveillance

In this study, we investigated the impact of cigarette smoke on tumor immune surveillance and its consequences to lung tumor burden in a murine lung metastasis model. Cigarette smoke exposure significantly increased the numbers of lung metastases following B16-MO5 melanoma challenge. This effect was...

Celý popis

Uložené v:
Podrobná bibliografia
Vydané v:Journal of Immunology Ročník 178; číslo 2; s. 936 - 943
Hlavní autori: Lu, Ling-Min, Zavitz, Caleb C J, Chen, Biao, Kianpour, Sussan, Wan, Yonghong, Stämpfli, Martin R
Médium: Journal Article
Jazyk:English
Vydavateľské údaje: United States 15.01.2007
Predmet:
Animals
Antigens, CD - metabolism
Antigens, Differentiation, T-Lymphocyte - metabolism
Cell Line, Tumor
Dendritic Cells - immunology
DNA-Binding Proteins - deficiency
DNA-Binding Proteins - genetics
DNA-Binding Proteins - metabolism
Female
Immunologic Surveillance - drug effects
Immunologic Surveillance - immunology
Interleukin-12 - deficiency
Interleukin-12 - genetics
Interleukin-12 - metabolism
Killer Cells, Natural - drug effects
Killer Cells, Natural - immunology
Lectins, C-Type
Liver Neoplasms - metabolism
Liver Neoplasms - pathology
Liver Neoplasms - secondary
Lung Neoplasms - immunology
Lung Neoplasms - metabolism
Lung Neoplasms - pathology
Lung Neoplasms - secondary
Lymphocyte Activation - immunology
Mice
Mice, Knockout
Nicotiana - adverse effects
Smoke - adverse effects
T-Lymphocytes, Cytotoxic - immunology
ISSN:0022-1767, 1365-2567
On-line prístup:Získať plný text
Tagy: Pridať tag
Žiadne tagy, Buďte prvý, kto otaguje tento záznam!
Popis
Shrnutí:In this study, we investigated the impact of cigarette smoke on tumor immune surveillance and its consequences to lung tumor burden in a murine lung metastasis model. Cigarette smoke exposure significantly increased the numbers of lung metastases following B16-MO5 melanoma challenge. This effect was reversible; we observed significantly fewer tumor nodules following smoking cessation. Using RAG2(-/-) and RAG2(-/-)gamma(c)(-/-) mice, we provide strong evidence that increased tumor incidence was NK cell dependent. Furthermore, we show that cigarette smoke suppressed NK activation and attenuated NK CTL activity, without apparent effect on activating or inhibitory receptor expression. Finally, activation of NK cells through bone marrow-derived dendritic cells conferred protection against lung metastases in smoke-exposed mice; however, protection was not as efficacious as in sham-exposed mice. To our knowledge, this is the first experimental evidence showing that cigarette smoke impairs NK cell-dependent tumor immune surveillance and that altered immunity is associated with increased tumor burden. Our findings suggest that altered innate immunity may contribute to the increased risk of cancer in smokers.
Bibliografia:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:0022-1767
1365-2567
DOI:10.4049/jimmunol.178.2.936