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

• Published in: Digestive diseases and sciences 2010-05, Vol.55 (5), p.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: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal - adverse effects; Antibodies, Monoclonal - therapeutic use; Biochemistry; Biological and medical sciences; Biopsy; Cause of Death; Colitis - chemically induced; Colitis - diagnosis; Colitis - immunology; Feeding. Feeding behavior; Female; Forkhead Transcription Factors - immunology; Fundamental and applied biological sciences. Psychology; Gastroenterology; Hepatology; Humans; Immunomodulators; Ipilimumab; Male; Medical sciences; Medicine; Medicine & Public Health; Melanoma - drug therapy; Melanoma - immunology; Middle Aged; Oncology; Original Article; Pharmacology. Drug treatments; Prostatic Neoplasms - drug therapy; Prostatic Neoplasms - immunology; Randomized Controlled Trials as Topic; Transplant Surgery; Treatment Outcome; Vertebrates: anatomy and physiology, studies on body, several organs or systems
• 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 (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.