A dual role for the immune response in a mouse model of inflammation-associated lung cancer

Michael Dougan, Danan Li, Donna Neuberg, Martin Mihm, Paul Googe, Kwok Kin Wong, Glenn Dranoff

Research output: Contribution to journalArticle

60 Citations (Scopus)

Abstract

Lung cancer is the leading cause of cancer death worldwide. Both principal factors known to cause lung cancer, cigarette smoke and asbestos, induce pulmonary inflammation, and pulmonary inflammation has recently been implicated in several murine models of lung cancer. To further investigate the role of inflammation in the development of lung cancer, we generated mice with combined loss of IFN-γ and the β-common cytokines GM-CSF and IL-3. These immunodeficient mice develop chronic pulmonary inflammation and lung tumors at a high frequency. Examination of the relationship between these tumors and their inflammatory microenvironment revealed a dual role for the immune system in tumor development. The inflammatory cytokine IL-6 promoted optimal tumor growth, yet wild-type mice rejected transplanted tumors through the induction of adaptive immunity. These findings suggest a model whereby cytokine deficiency leads to oncogenic inflammation that combines with defective antitumor immunity to promote lung tumor formation, representing a unique system for studying the role of the immune system in lung tumor development.

Original languageEnglish (US)
Pages (from-to)2436-2446
Number of pages11
JournalJournal of Clinical Investigation
Volume121
Issue number6
DOIs
StatePublished - Jun 1 2011

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Lung Neoplasms
Inflammation
Neoplasms
Pneumonia
Cytokines
Lung
Immune System
Interleukin-3
Asbestos
Adaptive Immunity
Granulocyte-Macrophage Colony-Stimulating Factor
Smoke
Tobacco Products
Cause of Death
Immunity
Interleukin-6
Growth

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

A dual role for the immune response in a mouse model of inflammation-associated lung cancer. / Dougan, Michael; Li, Danan; Neuberg, Donna; Mihm, Martin; Googe, Paul; Wong, Kwok Kin; Dranoff, Glenn.

In: Journal of Clinical Investigation, Vol. 121, No. 6, 01.06.2011, p. 2436-2446.

Research output: Contribution to journalArticle

Dougan, Michael ; Li, Danan ; Neuberg, Donna ; Mihm, Martin ; Googe, Paul ; Wong, Kwok Kin ; Dranoff, Glenn. / A dual role for the immune response in a mouse model of inflammation-associated lung cancer. In: Journal of Clinical Investigation. 2011 ; Vol. 121, No. 6. pp. 2436-2446.
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