Effects of immune suppression for transplantation on inflammatory colorectal cancer progression

Abstract

BackgroundUlcerative 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.MethodsWe 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.ResultsAll 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.ConclusionsPatients 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.

One-Time Fecal Immunochemical Screening for Advanced Colorectal Neoplasia in Patients with CKD (DETECT Study)

“…However, progression from adenoma to carcinoma may be hastened in the context of immunosuppression (as in the case of kidney transplantation) and persistent inflammation associated with uremia. 4 Performing work-up colonoscopies in all participants regardless of the index test results may mitigate the issue of differential verification bias, but it would be unethical to conduct potentially harmful and unnecessary investigations in individuals who are at risk of serious complications. Nevertheless, to overcome this limitation, performance characteristics of FIT to detect colorectal cancer, a more robust indicator, have been reported separately.…”

“…1 Sydney School of Public Health, Faculty of Medicine and Health, 19 School of Mathematics and Statistics, and 17 Charles Perkins Centre, The University of Sydney, Sydney, Australia; 2 Centre for Transplant and Renal Research, and 4 Department of Gastroenterology, Westmead Hospital, Westmead, New South Wales, Australia; 5 Gastroenterology Department, Hospital Clinic of Barcelona, University of Barcelona, Barcelona, Spain; 8 Department of Renal Medicine, Gosford Hospital, Gosford, Australia; 10 Department of Renal Medicine, Sir Charles Gairdner Hospital, Perth, Australia; 11 Faculty of Medicine, University of Toronto, Ontario, Canada; 12 Department of Nephrology and Kidney Transplantation, Clinical and Provincial Hospital of Barcelona, Barcelona, Spain; 13 Department of Nephrology and Kidney Transplantation, Christchurch Hospital, Christchurch, New Zealand; 15 Department of Renal Medicine, Concord Repatriation General Hospital, Concord, Australia; 16 Department of Renal Medicine, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia; 18…”

“…loss of cancer immune editing resulting from chronic immunosuppression. 4 Cancer outcomes are poor in those with CKD. 5 Five-year survival after a colorectal cancer diagnosis is ,50% for kidney transplant recipients and ,30% for patients on dialysis.…”

Foremost Concepts in Mechanisms of De Novo Post-Liver Transplantation Malignancy

“…A study by Angriman et al demonstrated that a reduced Treg subpopulation in mice receiving TAC, cyclosporine, and mTOR inhibitors correlated with the reduced pro-tumorigenic effect of these cells [34]. High expression of IL-2Rβ and IL-2Rγ was detected in NK cells, monocytes, macrophages, and resting CD4+ and resting CD8+ T cells.…”