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

• Published in: The Journal of clinical investigation Vol. 123; no. 6; pp. 2509 - 2522
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: United States American Society for Clinical Investigation 01.06.2013
• Subjects: Adenocarcinoma - immunology; Adenocarcinoma - metabolism; Adenocarcinoma - mortality; Animals; Carcinoma, Lewis Lung - immunology; Carcinoma, Lewis Lung - metabolism; Cell Line, Tumor; Cellular signal transduction; Chemokines - genetics; Chemokines - metabolism; Development and progression; Gene Expression - immunology; Genetic aspects; 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; Neoplasm Transplantation; Neutrophils - immunology; Neutrophils - metabolism; NF-kappa B - metabolism; Oligonucleotide Array Sequence Analysis; Physiological aspects; Signal Transduction; T cells; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; Transcription factors; Transcriptome - immunology; Tumors; United States
• ISSN: 0021-9738; 1558-8238
• DOI: 10.1172/JCI67250

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.