The association of infiltrating lymphocytes in androgen ablation induced apoptosis of prostate tumours

• Main Author: Walker, Tristan J.
• Language: English
• Published: 2009
• Online Access: http://hdl.handle.net/2429/16799

Prostate cancer has a high incidence and mortality rate, with currently no curative treatment for advanced disease. Both the gland and the tumour are androgen dependent; therefore, the removal of androgens, known clinically as hormone ablation therapy, is the most effective treatment, and is thought to force secretory epithelial cells, as well as the cancerous tissue, to undergo apoptosis. Unfortunately, the effects of the hormone ablative therapy are temporary and prostate cancer will recur in an untreatable androgen independent phenotype. The underlying molecular mechanisms involved in prostate cancer progression and the effects of androgen ablation are poorly understood, and the process by which the cancer is cleared, post-androgen ablation, has never been clearly elucidated. This study proposes that, contrary to present theorem, androgen ablation itself is insufficient to induce apoptosis; rather, the apoptotic reaction is facilitated by immune factors including the presence of immune cells at the tumour site. Observational data was used in conjunction with microarray experiments and immunohistochemistry to identify underlying gene expression and immune cell components of tumours grown in hosts with varying states of immunocompentency. We demonstrate that the immunocompetency of the host affects the rate of tumour regression post androgen ablation. Our results show that a tumour in a host with a functional immune system will regress faster and reach its nadir point sooner than in B- or T-cell deficient animals. Furthermore, lymphocyte infiltration significantly changes at the point at which the tumour reaches its lowest point. This correlates with gene expression studies showing a shift towards up-regulating genes related to antigen presentation and immune function. Immunohistochemistry on human tissue samples analyzed from radical prostatectomies also show a marked increase in lymphocyte infiltration post androgen ablation. A better understanding of the tumour environment and effecter immune factors present will provide additional clinical strategies and therapeutic targets to better facilitate androgen ablation therapy. === Medicine, Faculty of === Medical Genetics, Department of === Graduate