Erschienen in:
01.05.2010 | Original Article
Refractory Colitis Following Anti-CTLA4 Antibody Therapy: Analysis of Mucosal FOXP3+ T Cells
verfasst von:
James D. Lord, Robert C. Hackman, Amanda Moklebust, John A. Thompson, Celestia S. Higano, Deborah Chielens, Gideon Steinbach, George B. McDonald
Erschienen in:
Digestive Diseases and Sciences
|
Ausgabe 5/2010
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Abstract
Ipilimumab is a humanized antibody to CTLA4 and is used to treat cancers refractory to conventional treatment. We treated 21 patients with refractory melanoma or prostate cancer with anti-CTLA4 antibody (ipilimumab), with subsequent development of significant colitis in nine cases. Two of these nine did not respond rapidly to high-dose (2 mg kg−1 day−1) glucocorticoids or infliximab. They required additional immunosuppression, and one ultimately died of opportunistic infection, representing a more refractory course than has previously been described complicating ipilimumab therapy. Both patients had received radiation to the pelvis for prostate cancer less than 1 year prior to receiving ipilimumab. We performed immunohistochemical analysis of colon biopsies from ipilimumab recipients to determine if colitis correlates with depletion of intramucosal FOXP3+ regulatory T cells (Tregs), which normally express CTLA4. However, we found no evidence of FOXP3+ T cell depletion in any of the nine patients who developed colitis.