Effects of immune suppression for transplantation on inflammatory colorectal cancer progression

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