title: Clinical investigation of the role of interleukin-4 and interleukin-13 in the evolution of prostate cancer.
abstract: Prostate cancer is the most common cancer in men, both in the USA and Europe. Although incurable, metastatic disease can often be controlled for years with anti-androgen therapy. Once the disease becomes castrate resistant, the median survival is 18 months. There is growing evidence that the immune system, and in particular cytokines, play an important role in prostate cancer immunosurveillance and progression. Here, we have undertaken a clinical investigation of the role of two closely related cytokines, IL-4 and IL-13 in prostate cancer. In the largest series studied to date, we show that serum IL-4, but not IL-13 is significantly elevated in castrate resistant, compared to androgen sensitive disease. Notably however, serum IL-4 levels are also raised in patients with benign prostatic disease. Analysis of benign and malignant prostate tissue demonstrates that the source of IL-4 is epithelial cells rather than infiltrating leukocytes. Together, our data are consistent with a dual role for IL-4 in prostate cancer development. In benign disease, our data add to the evidence that IL-4 serves a protective role. By contrast, the data support a direct role for IL-4 in the progression of prostate cancer from androgen responsive, to advanced castrate-resistant disease.
authors.affiliation: Department of Research Oncology, King's Health Partners Integrated Cancer Center, King's College London, Guy's Hospital Campus, Great Maze Pond, London SE1 9RT, UK. sophie.burbridge@kcl.ac.uk.
authors.forename: Robert
authors.initials: R
authors.lastname: Goldstein
authors.forename: Charles
authors.initials: C
authors.lastname: Hanley
authors.forename: Jonathan
authors.initials: J
authors.lastname: Morris
authors.forename: Declan
authors.initials: D
authors.lastname: Cahill
authors.forename: Ashish
authors.initials: A
authors.lastname: Chandra
authors.forename: Peter
authors.initials: P
authors.lastname: Harper
authors.forename: Simon
authors.initials: S
authors.lastname: Chowdhury
authors.forename: John
authors.initials: J
authors.lastname: Maher
authors.forename: Sophie
authors.initials: S
authors.lastname: Burbridge