| First Author | Rizzo A | Year | 2014 |
| Journal | Carcinogenesis | Volume | 35 |
| Issue | 7 | Pages | 1536-46 |
| PubMed ID | 24480808 | Mgi Jnum | J:211591 |
| Mgi Id | MGI:5575711 | Doi | 10.1093/carcin/bgu027 |
| Citation | Rizzo A, et al. (2014) Smad7 induces plasticity in tumor-infiltrating Th17 cells and enables TNF-alpha-mediated killing of colorectal cancer cells. Carcinogenesis 35(7):1536-46 |
| abstractText | Transforming growth factor-beta (TGF-beta) is deeply involved in colorectal cancer development and the disruption of the TGF-beta signaling in dysplastic cells is required for tumor to grow. Nevertheless, tumor cells express TGF-beta to escape the immune surveillance mediated by T cells. T-cell expression of Smad7, an intracellular inhibitor of the TGF-beta signaling, protects against colitis-associated colorectal cancer. However, whether Smad7 in T cells might influence colorectal cancer growth independently of chronic inflammation and which T-cell subset is involved in this process is unknown. To address this issue, T-cell-specific Smad7 transgenic mice and wild-type (WT) littermates were subcutaneously transplanted with syngenic MC38 colon carcinoma cells. Smad7Tg mice were resistant to tumor development compared with WT mice and protection was dependent on CD4(+) T cells. Smad7 expression in T cells increased the number of tumor-infiltrating Tbet/ROR-gamma-t double-positive CD4 T cells characterized by the expression of tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma but lower IL17A. The low expression of IL17A caused by the Smad7 expression in tumor-infiltrating CD4(+) T cells enabled the TNF-alpha-mediated killing of cancer cells both in vitro and in vivo, thus indicating that the Smad7-mediated plastic effect on T-cell phenotype induces protection against colorectal cancer. |
