Anti-CTLA-4 therapy in bladder cancer patients alters immune responses by increasing IFNγ production and decreasing the CD4⁺FOXP3 ⁺ regulatory T cells in the tumor microenvironment

CTLA-4 blockade is an active immunotherapeutic strategy in clinical trials for which measurable tumor responses, including durable complete responses, have been reported in some patients with metastatic disease. To date no consistent immunological changes associated either with drug administration or clinical benefit have been demonstrated. Here we present data from a neoadjuvant clinical trial demonstrating that anti-CTLA-4 therapy increases IFN-γ production by circulating CD4 T cells as compared to levels found pre-therapy or in healthy donors. Surgical specimens of tumor tissues from patients who were treated with anti-CTLA-4 antibody had similar immunological changes and furthermore decreased CD4⁺FOXP3⁺ T cells when compared with malignant tissues. These findings provide insight into the immunologic impact of CTLA-4 blockade that will be useful in understanding its mechanisms of action and optimizing its clinical development as an effective cancer immunotherapy.