In contrast with other strategies,
immunotherapy is the only treatment aimed at empowering the immune system to increase the response against
tumor growth.
Immunotherapy has a role in the treatment of
bladder cancer (BC) due to these
tumors' high
tumor mutational burden (TMB) and mostly prominent immune infiltrate. The
therapy or combination has to be adjusted to the
tumor's immunobiology. Recently, a new class of immunotherapeutic agents,
immune checkpoint inhibitors (ICI), has shown potential in increasing treatment chances for patients with
genitourinary cancers, improving their oncological outcomes. The clinical efficacy of ICI has been shown in both the first-line treatment of
cisplatin-ineligible patients, with
programmed death ligand 1 (PD-L1)-positive
tumors (
atezolizumab,
pembrolizumab), and in second-line settings, for progression after
platinum-based
chemotherapy (
atezolizumab,
pembrolizumab, and
nivolumab for FDA and EMA;
durvalumab and
avelumab for FDA alone). Predicting the response to ICI is important since only a subset of patients undergoing ICI
therapy develop a concrete and lasting response. Most of the patients require a different
therapy or
therapy combination to achieve
tumor control. The
cancer immunity cycle provides a conceptual framework to assist
therapy selection.
Biomarkers to predict response to ICI must identify where the
cancer immunity cycle is disrupted. We reviewed the current knowledge on ICI treatment in BC, going from basic science to current data and available clinical evidence. Secondly, a critical analysis of published data is provided, and an original panel of
biomarkers able to predict response to ICI treatment, based on
tumor-specific immune profiling, is proposed.