Department of Immunology, Moffitt Cancer Center, Tampa, Florida 33612, USA.
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.
NF-κB 在许多癌症类型中持续激活，是肿瘤相关炎症、肿瘤生长和转移的潜在关键介质。我们研究了癌细胞 NF-κB 活性在 T 细胞介导的抗肿瘤反应中的作用。在通过模型抗原表达或给予抗肿瘤疫苗使肿瘤具有免疫原性的情况下，我们发现高 NF-κB 活性导致小鼠肿瘤排斥和/或生长抑制。使用全基因组 RNA 表达微阵列，我们证明 NF-κB 增强了几种 T 细胞趋化因子的表达，包括 Ccl2，而 CCL2 表达的降低与小鼠肺癌模型中肿瘤生长的增强相关。为了研究 NF-κB 在人类肺癌中的功能，我们在人类肺腺癌细胞系中鉴定了一个与 NF-κB 活性水平相关的基因表达特征。在患者肿瘤样本中，整个肺肿瘤 NF-κB 活性与 T 细胞浸润强烈相关，但与癌细胞增殖无关。因此，这些结果表明 NF-κB 活性在小鼠和人类肺癌中介导免疫监视并促进抗肿瘤 T 细胞反应。
