Refractory Colitis Following Anti-CTLA4 Antibody Therapy: Analysis of Mucosal FOXP3 super(+) T Cells

• Published in: Digestive diseases and sciences Vol. 55; no. 5; pp. 1396 - 1405
• Main Authors: Lord, James D, Hackman, Robert C, Moklebust, Amanda, Thompson, John A, Higano, Celestia S, Chielens, Deborah, Steinbach, Gideon, McDonald, George B
• Format: Journal Article
• Language: English
• Published: 01-05-2010
• ISSN: 0163-2116; 1573-2568
• DOI: 10.1007/s10620-009-0839-8

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 (2mgkg super(-1)d ay super(-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 1year prior to receiving ipilimumab. We performed immunohistochemical analysis of colon biopsies from ipilimumab recipients to determine if colitis correlates with depletion of intramucosal FOXP3 super(+) regulatory T cells (Tregs), which normally express CTLA4. However, we found no evidence of FOXP3 super(+) T cell depletion in any of the nine patients who developed colitis.