Lung tumor NF-κB signaling promotes T cell-mediated immune surveillance

Emily L. Hopewell, Weipeng Zhao, William J. Fulp, Crystina C. Bronk, Alexis S. Lopez, Michael Massengill, Scott Antonia, Esteban Celis, Eric B. Haura, Steven A. Enkemann, Dung Tsa Chen, Amer A. Beg

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Abstract

NF-κB is constitutively activated in many cancer types and is a potential key mediator of tumor-associated inflammation, tumor growth, and metastasis. We investigated the role of cancer cell NF-κB activity in T cell-mediated antitumor responses. In tumors rendered immunogenic by model antigen expression or following administration of antitumor vaccines, we found that high NF-κB activity leads to tumor rejection and/or growth suppression in mice. Using a global RNA expression microarray, we demonstrated that NF-κB enhanced expression of several T cell chemokines, including Ccl2, and decreased CCL2 expression was associated with enhanced tumor growth in a mouse lung cancer model. To investigate NF-κB function in human lung tumors, we identified a gene expression signature in human lung adenocarcinoma cell lines that was associated with NF-κB activity level. In patient tumor samples, overall lung tumor NF-κB activity was strongly associated with T cell infiltration but not with cancer cell proliferation. These results therefore indicate that NF-κB activity mediates immune surveillance and promotes antitumor T cell responses in both murine and human lung cancer.

Original languageEnglish (US)
Pages (from-to)2509-2522
Number of pages14
JournalJournal of Clinical Investigation
Volume123
Issue number6
DOIs
StatePublished - Jun 3 2013

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T-Lymphocytes
Lung
Neoplasms
Lung Neoplasms
Growth
Transcriptome
Chemokines
Vaccines
Cell Proliferation
RNA
Neoplasm Metastasis
Inflammation
Antigens
Cell Line

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Hopewell, E. L., Zhao, W., Fulp, W. J., Bronk, C. C., Lopez, A. S., Massengill, M., ... Beg, A. A. (2013). Lung tumor NF-κB signaling promotes T cell-mediated immune surveillance. Journal of Clinical Investigation, 123(6), 2509-2522. https://doi.org/10.1172/JCI67250

Lung tumor NF-κB signaling promotes T cell-mediated immune surveillance. / Hopewell, Emily L.; Zhao, Weipeng; Fulp, William J.; Bronk, Crystina C.; Lopez, Alexis S.; Massengill, Michael; Antonia, Scott; Celis, Esteban; Haura, Eric B.; Enkemann, Steven A.; Chen, Dung Tsa; Beg, Amer A.

In: Journal of Clinical Investigation, Vol. 123, No. 6, 03.06.2013, p. 2509-2522.

Research output: Contribution to journalArticle

Hopewell, EL, Zhao, W, Fulp, WJ, Bronk, CC, Lopez, AS, Massengill, M, Antonia, S, Celis, E, Haura, EB, Enkemann, SA, Chen, DT & Beg, AA 2013, 'Lung tumor NF-κB signaling promotes T cell-mediated immune surveillance', Journal of Clinical Investigation, vol. 123, no. 6, pp. 2509-2522. https://doi.org/10.1172/JCI67250
Hopewell EL, Zhao W, Fulp WJ, Bronk CC, Lopez AS, Massengill M et al. Lung tumor NF-κB signaling promotes T cell-mediated immune surveillance. Journal of Clinical Investigation. 2013 Jun 3;123(6):2509-2522. https://doi.org/10.1172/JCI67250
Hopewell, Emily L. ; Zhao, Weipeng ; Fulp, William J. ; Bronk, Crystina C. ; Lopez, Alexis S. ; Massengill, Michael ; Antonia, Scott ; Celis, Esteban ; Haura, Eric B. ; Enkemann, Steven A. ; Chen, Dung Tsa ; Beg, Amer A. / Lung tumor NF-κB signaling promotes T cell-mediated immune surveillance. In: Journal of Clinical Investigation. 2013 ; Vol. 123, No. 6. pp. 2509-2522.
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