Smad7 induces plasticity in tumor-infiltrating Th17 cells and enables TNF-alpha-mediated killing of colorectal cancer cells

Rizzo A, De Mare V, Rocchi C, Stolfi C, Colantoni A, Neurath M, Macdonald TT, Pallone F, Monteleone G, Fantini MC (2014)

Publication Type: Journal article

Publication year: 2014

Journal

Carcinogenesis Oxford University Press (OUP): Policy B - Oxford Open Option B

Book Volume: 35

Pages Range: 1536-46

Journal Issue: 7

DOI: 10.1093/carcin/bgu027

Abstract

Transforming growth factor-beta (TGF-?) is deeply involved in colorectal cancer development and the disruption of the TGF-? signaling in dysplastic cells is required for tumor to grow. Nevertheless, tumor cells express TGF-? to escape the immune surveillance mediated by T cells. T-cell expression of Smad7, an intracellular inhibitor of the TGF-? 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-?-t double-positive CD4 T cells characterized by the expression of tumor necrosis factor-alpha (TNF-?) 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-?-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.

Authors with CRIS profile

Markus Neurath Lehrstuhl für Innere Medizin I

Involved external institutions

Università degli Studi di Roma 'Tor Vergata' IT Italy (IT) Queen Mary University of London GB United Kingdom (GB)

How to cite

APA:

Rizzo, A., De Mare, V., Rocchi, C., Stolfi, C., Colantoni, A., Neurath, M.,... Fantini, M.C. (2014). Smad7 induces plasticity in tumor-infiltrating Th17 cells and enables TNF-alpha-mediated killing of colorectal cancer cells. Carcinogenesis, 35(7), 1536-46. https://doi.org/10.1093/carcin/bgu027

MLA:

Rizzo, Angelamaria, et al. "Smad7 induces plasticity in tumor-infiltrating Th17 cells and enables TNF-alpha-mediated killing of colorectal cancer cells." Carcinogenesis 35.7 (2014): 1536-46.

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