Local and systhemic immunotherapy for bladder cancer: from bench to bedside

Therapeutic approaches for treatment of urothelial transitional cell carcinoma based on immune system modulation, as well as the contribution of introvesical Bacillus de Calmette-Guerin (BCG) and the recent incorporation of checkpoint inhibitors had found irrefutable proofs of concept for the indication of antitumoral immunontherapy in such tumors. Its extension and development at the present time covers all the locations of the wide spectrum of presentation and evolution of these tumors. Nowadays, apart for the low grade non muscle-invasive tumors, we are facing an unpredictable development of antitumoral immunotherapy in bladder cancer not only as an option in the primary treatment, but also in other scenarios such as non-responders when it comes to BCG, or the situation of ineligibility for systemic chemotherapy indication. The main objective of this review article is trying to translate the current basic mechanisms involved in different phases of transitional cell carcinomas antitumoral response, regardless of whether they are muscle-invasive or not, and to establish the rationale for their therapeutic intravesical or systemic administration. The role of the interactions established between urothelial tumor cells and the cellular and molecular elements of the immune system of patients is described, incorporating the relevant and recent advances in immunobiology and the molecular characterization of these tumors that will undoubtedly introduce far-reaching modifications in therapeutic regimes that will contrast with the traditional options available. Investigational lines that are already active in the clinical research phase with BCG and, checkpoints inhibitors of the immune response are also analyzed, highlighting the need to find predictive response markers as a real option for treatments personalization. The approach to the knowledge of the individual reactivity of the immune system of each patient as a determining factor to achieve it is proposed.