| The immune system is an important defense mechanism against cancer and is often dysfunctional in patients with malignancies. The central regulator of the anti-cancer adaptive immune response is the T lymphocyte. T lymphocyte activation requires the completion of a carefully orchestrated series of specific steps that can be preempted or disrupted by any number of critical events. Particularly important is the provision of a costimulatory signal, the binding of accessory molecules on the antigen presenting cell to receptors on the T lymphocyte. Though costimulatory signals were traditionally envisioned as a T lymphocyte-activating events, recent discoveries have highlighted their duality: they can be either stimulatory (costimulation) or inhibitory (coinhibition). In this thesis I examine programmed death ligand-1 (PD-L1) mediated coinhibition as a mechanism for bladder cancer stage progression. I also present evidence for the role of PD-L1 in granulomatous inflammation in a wide variety of granulomatous disorders. Lastly, I discuss the development of a novel diagnostic test for detecting soluble PD-L1 present in biological fluids and demonstrate its sensitivity, specificity and calibration in patients with cancer. |
