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

J Clin Invest. 2013 Jun;123(6):2509-22. doi: 10.1172/JCI67250. Epub 2013 May 1.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / immunology*
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / mortality
  • Animals
  • Carcinoma, Lewis Lung / immunology*
  • Carcinoma, Lewis Lung / metabolism
  • Cell Line, Tumor
  • Chemokines / genetics
  • Chemokines / metabolism
  • Gene Expression / immunology
  • Graft Rejection
  • HEK293 Cells
  • Humans
  • I-kappa B Kinase / metabolism
  • Immunologic Factors / genetics
  • Immunologic Factors / metabolism
  • Immunologic Surveillance
  • Lung Neoplasms / immunology*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / mortality
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • NF-kappa B / metabolism*
  • Neoplasm Transplantation
  • Neutrophils / immunology
  • Neutrophils / metabolism
  • Oligonucleotide Array Sequence Analysis
  • Signal Transduction*
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism
  • Transcriptome / immunology


  • Chemokines
  • Immunologic Factors
  • NF-kappa B
  • I-kappa B Kinase
  • Ikbkb protein, mouse

Associated data

  • GEO/GSE44619