title: Lung tumor NF-κB signaling promotes T cell-mediated immune surveillance.
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.
authors: Department of Immunology, Moffitt Cancer Center, Tampa, Florida 33612, USA.
authors: Emily L
authors: EL
authors: Hopewell
authors: Weipeng
authors: W
authors: Zhao
authors: William J
authors: WJ
authors: Fulp
authors: Crystina C
authors: CC
authors: Bronk
authors: Alexis S
authors: AS
authors: Lopez
authors: Michael
authors: M
authors: Massengill
authors: Scott
authors: S
authors: Antonia
authors: Esteban
authors: E
authors: Celis
authors: Eric B
authors: EB
authors: Haura
authors: Steven A
authors: SA
authors: Enkemann
authors: Dung-Tsa
authors: DT
authors: Chen
authors: Amer A
authors: AA
authors: Beg
mesh_terms: D000230:Adenocarcinoma / Q000276:immunology* / Q000378:metabolism / Q000401:mortality; D000818:Animals; D018827:Carcinoma, Lewis Lung / Q000276:immunology* / Q000378:metabolism; D045744:Cell Line, Tumor; D018925:Chemokines / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression / Q000276:immunology; D006084:Graft Rejection; D057809:HEK293 Cells; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism; D007155:Immunologic Factors / Q000235:genetics / Q000378:metabolism; D007157:Immunologic Surveillance; D008175:Lung Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000401:mortality; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism*; D009368:Neoplasm Transplantation; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D059467:Transcriptome / Q000276:immunology
chemical_list: D018925:Chemokines; D007155:Immunologic Factors; D016328:NF-kappa B; D051550:I-kappa B Kinase; C496562:Ikbkb protein, mouse
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