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

Publication Type:

Journal Article

Source:

Digestive diseases and sciences, Volume 55, Issue 5, p.1396-405 (2010)

Keywords:

2010, Adult, Aged, Aged, 80 and over, Antibodies, Monoclonal, Biopsy, Cause of Death, Center-Authored Paper, Clinical Research Division, Colitis, Female, Forkhead Transcription Factors, Humans, Male, MELANOMA, Middle Aged, Prostatic Neoplasms, Public Health Sciences Division, Randomized Controlled Trials as Topic, Treatment Outcome

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.