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

Effects of immune suppression for transplantation on inflammatory colorectal cancer progression

Angriman, Imerio;Furian, Lucrezia;Scarpa, Melania;Fassan, Matteo;Porzionato, Andrea;Kotsafti, Andromachi;SAADEH, LUCA MARIA;Silvestre, Cristina;De Caro, Raffaele;Carraro, Amedeo;TEDESCHI, UMBERTO;Bardini, Romeo;Rigotti, Paolo;Rugge, Massimo;Castoro, Carlo;Castagliuolo, Ignazio;
2018

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
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11577/3272203
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