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

Dig Dis Sci. 2010 May;55(5):1396-405. doi: 10.1007/s10620-009-0839-8. Epub 2009 Jun 9.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal / adverse effects*
  • Antibodies, Monoclonal / therapeutic use
  • Biopsy
  • Cause of Death
  • Colitis / chemically induced*
  • Colitis / diagnosis
  • Colitis / immunology
  • Female
  • Forkhead Transcription Factors / immunology
  • Humans
  • Ipilimumab
  • Male
  • Melanoma / drug therapy*
  • Melanoma / immunology
  • Middle Aged
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / immunology
  • Randomized Controlled Trials as Topic
  • Treatment Outcome


  • Antibodies, Monoclonal
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Ipilimumab