Concurrent decrease in IL-10 with development of immune-related adverse events in a patient treated with anti-CTLA-4 therapy.
Cancer Immun. 2008 May 27;8:9.
Sun J, Schiffman J, Raghunath A, Ng Tang D, Chen H, Sharma P.
Department of Genitourinary Medical Oncology, The University of Texas, M. D. Anderson Cancer Center, Houston, TX, USA.
The cytotoxic T lymphocyte antigen-4 (CTLA-4) molecule on T cells acts to maintain homeostasis by regulating the proliferation of recently activated T cells. Blockade of CTLA-4 by anti-CTLA-4 antibody enhances T cell responses and has elicited significant tumor regression in some cancer patients. Clinical trials are ongoing to investigate the efficacy of anti-CTLA-4 antibody as a cancer therapeutic. Reports from several clinical trials have documented the occurrence of adverse events in patients treated with anti-CTLA-4 antibody which have some similarities with autoimmune conditions and have been termed immune-related adverse events (irAEs). Most irAEs are reversible with corticosteroid therapy. Some investigators suggest that irAEs occur in the same patients who have anti-tumor responses as a result of the anti-CTLA-4 antibody. Immunologic mechanisms to explain why irAEs occur in some patients have not been reported. Here we report that bladder cancer patients treated with anti-CTLA-4 antibody have increased levels of the Th1 cytokine IFN-gamma detected in plasma samples. Although IFN-gamma is a potent anti-tumor and inflammatory cytokine, increased levels of IFN-gamma were not associated with irAEs in our patients. However, in one patient who experienced an irAE consisting of ischemic papillopathy and optic neuritis, we documented high pre-therapy levels of the Th2 cytokine IL-10 which decreased after treatment with anti-CTLA-4 antibody. The decrease in plasma IL-10 concentration coincided with the patient's irAE. We propose that decreased levels of IL-10 after treatment with anti-CTLA-4 therapy may be responsible for irAEs in some patients and needs to be further investigated in larger studies. |
