Chromosome 1 open reading frame 190 promotes activation of NF-κB canonical pathway and resistance of dendritic cells to tumor-associated inhibition in vitro.

Tumor-associated dendritic cells (DCs) often induce T cell anergy or deletion and regulatory T cells instead of antitumor immunity. Although many tumor-associated Ags have been found, there is still no effective vaccine for cancer. Thus, novel rational strategies to enhance the immunogenicity of cancer-specific Ags are needed. Chromosome 1 open reading frame 190 (c1orf190), a gene that encodes a 239-aa hypothetical protein and contains multiple kinase phosphorylation sites, has a wide relationship with multiple signaling pathway molecules and can be regulated by multiple factors, such as TLR ligands. In this study, we demonstrate that c1orf190 can activate NF-κB, drive the production of cytokines, and promote the Ag-presenting function and the priming ability of DCs. Furthermore, c1orf190 can promote resistance of DCs to tumor-associated inhibition not only in the Ag-presenting function but also in the priming ability to induce Ag-specific T lymphocytes. Thus, c1orf190, an NF-κB activator, may be a candidate gene for regulating the function of DCs to resist tumor-associated factor-mediated dysfunction. We also found that c1orf190-mediated cytokine release is achieved by activating the canonical but not the noncanonical NF-κB pathway.