Urologic malignancies including prostate, kidney, and bladder cancer are common diseases. Despite advances in traditional treatment modalities for these malignancies, sequential cellular mutations often lead to resistance against therapeutic measures and eventual disease progression. An important factor in this process is the ability of cancer cells to evade the host immune system.
Under normal circumstances, the immune response provides a desirable profile for combating malignancy. T cells have excellent specificity due to their ability to recognize major histocompatibility complexes on the surface of cells. This allows for recognition of both intracellular and extracellular peptides. Additionally, T cells are able to produce memory, which allows for rapid and targeted response in the event of future recurrence.
Finally, T cells have the ability to adapt to the changing antigen profile of recurrent cancer cells. This is held in check by a series of stimulatory and co-inhibitory signals to prevent excessive immune activation, autoimmunity, and non-selective tissue destruction.
Cancer cells, as we have learned, often adopt a number of strategies to evade the host immune response. Upregulation of co-inhibitory signaling molecules such as programmed cell death ligand-1 (PD-L1) inhibits cell killing when interacting with programmed death 1 (PD-1) receptors on effector T-cells (figure 1).
Similarly, upregulation of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) leads to T-cell tolerance and evasion of the immune system (figure 2). The ability to restore immune recognition through antibody mediated checkpoint blockade has provided an appealing therapeutic target in the treatment of cancer and ushered FDA approval of several novel agents.
This article explores the current and potential future use of immunotherapy in prostate, kidney, and bladder cancer.
Next: Prostate cancer