Refractory colitis following anti-CTLA4 antibody therapy: analysis of mucosal FOXP3+ T cells.

Dig Dis Sci 2010 May 9;55(5):1396-405. Epub 2009 Jun 9.

Department of Medicine, University of Washington, Seattle, WA, USA.

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.

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http://dx.doi.org/10.1007/s10620-009-0839-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2904314PMC
May 2010
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