Lung tumor NF-?B signaling promotes T cell-mediated immune surveillance.

ABSTRACT: NF-?B 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-?B 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-?B activity leads to tumor rejection and/or growth suppression in mice. Using a global RNA expression microarray, we demonstrated that NF-?B 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-?B function in human lung tumors, we identified a gene expression signature in human lung adenocarcinoma cell lines that was associated with NF-?B activity level. In patient tumor samples, overall lung tumor NF-?B activity was strongly associated with T cell infiltration but not with cancer cell proliferation. These results therefore indicate that NF-?B activity mediates immune surveillance and promotes antitumor T cell responses in both murine and human lung cancer.

SUBMITTER: Hopewell EL 

PROVIDER: S-EPMC3668836 | biostudies-literature | 2013 Jun

REPOSITORIES: biostudies-literature