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- W4313373742 abstract "Abstract Background and aims Chronic colonic inflammation drives colon tumorigenesis. Chronic infection-associated inflammation causes T cell exhaustion/dysfunction. NF-kB is a molecular link between colonic inflammation and colorectal cancer. We aimed at testing the hypothesis that the p50 NF-kB (NF-kB1) regulates T cell dysfunction to promote colon tumor immune evasion and development. Methods Nfkb1 knock out (p50 KO), Nfkb1 KO chimera mice, Nfkb1 KO colon tumor cells were used to determine p50 NF-kB function in colon tumor development. RNA-Seq, chromatin immunoprecipitation, and electrophoresis mobility shift assay were used to elucidate molecular mechanism of NF-kB1 action. Flow cytometry was used to analyze cytotoxic T lymphocytes. Results p50 KO mice showed a significantly decrease in tumorigenesis. However, mice with p50 deficiency only in immune cells also exhibited a significant decrease in tumorigenesis, and p50-sufficient colon tumor cells also grew significantly slower in p50 KO mice than in WT mice. RNA-Seq identified Gzmb as a p50 NF-kB target gene. p50 KO mice have significantly higher tumor-infiltrating granzyme B+ CTLs than WT mice, and CTL granzyme B protein level is also significantly higher in p50 KO mice than in WT mice. A kB sequence element was identified at the Gzmb promoter and p50 NF-kB directly binds to this kB element in T cells to repress Gzmb expression. Conclusion NF-kB1 has opposing functions in tumor cells and T cells in vivo. The p50 NF-kB represses Gzmb expression to confer colon tumor-infiltrating CTL a dysfunctional phenotype to promote colon tumor immune evasion, resulting in enhanced colon tumorigenesis and growth." @default.
- W4313373742 created "2023-01-06" @default.
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- W4313373742 date "2020-05-01" @default.
- W4313373742 modified "2023-09-30" @default.
- W4313373742 title "NF-kB1 induces T cell dysfunction to promote colon tumorigenesis" @default.
- W4313373742 doi "https://doi.org/10.4049/jimmunol.204.supp.165.32" @default.
- W4313373742 hasPublicationYear "2020" @default.
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