Effects of immune suppression for transplantation on inflammatory colorectal cancer progression

Imerio Angriman, Lucrezia Furian, Melania Scarpa, Matteo Fassan, Susan Morgan, Andrea Porzionato, Andromachi Kotsafti, Luca Saadeh, Cristina Silvestre, Raffaele De Caro, Amedeo Carraro, Umberto Tedeschi, Romeo Bardini, Paolo Rigotti, Massimo Rugge, Carlo Castoro, Ignazio Castagliuolo, Marco Scarpa

Research output: Contribution to journalArticle

Abstract

Background: Ulcerative colitis patients and transplant recipients are at risk for colorectal cancer. Here, we show that immunosuppressive regimens for kidney transplants are associated with the progression of ulcerative colitis-related carcinogenesis. Methods: We describe the case of a patient diagnosed with colorectal cancer in ulcerative colitis while on immunosuppressive therapy for a kidney transplant. The immunological microenvironment of the cancer and its mutational status were analyzed, and a mouse colon cancer model was created to replicate the unique clinical conditions. AOM/DSS mice were randomized into seven experimental groups that received different immunosuppressants and an untreated control group to assess the frequencies of adenocarcinoma and high-grade dysplasia. Histopathology, immunohistochemistry, and flow cytometry were also performed on the harvested mouse colons. Results: All mice treated with an immunosuppressive regimen developed at least an adenoma, and several of those receiving anti-CD3, anti-CD8, and mycophenolate mofetil also developed adenocarcinomas. In contrast, mice receiving rapamycin did not develop adenocarcinomas, and the extent of high-grade dysplasia in those mice was similar to that in control mice. Conclusions: Patients with pre-neoplastic conditions, such as ulcerative colitis, who are undergoing a solid organ transplant might benefit from the use of mTOR inhibitors given their intrinsic anti-tumor properties.

Original languageEnglish
Article number46
JournalOncogenesis
Volume7
Issue number6
DOIs
Publication statusPublished - Jun 1 2018

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research

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  • Cite this

    Angriman, I., Furian, L., Scarpa, M., Fassan, M., Morgan, S., Porzionato, A., Kotsafti, A., Saadeh, L., Silvestre, C., De Caro, R., Carraro, A., Tedeschi, U., Bardini, R., Rigotti, P., Rugge, M., Castoro, C., Castagliuolo, I., & Scarpa, M. (2018). Effects of immune suppression for transplantation on inflammatory colorectal cancer progression. Oncogenesis, 7(6), [46]. https://doi.org/10.1038/s41389-018-0055-5