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Checkpoint inhibition in bladder cancer: Clinical expectations, current evidence, and proposal of future strategies based on a tumor-specific immunobiological approach.
Cancers 13:6016 (2021)
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.
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Publication type
Article: Journal article
Document type
Review
Keywords
Bcg Failure ; Bladder Cancer ; Cancer Immunoprofiling ; Checkpoint Inhibition ; Immunotherapy Biomarkers ; Randomized Clinical Trials ; Urological Research; Metastatic Urothelial Carcinoma; Cisplatin-ineligible Patients; Cd4(+) T-cells; Single-arm; Infiltrating Lymphocytes; Neoadjuvant Chemotherapy; Pd-l1 Blockade; Solid Tumors; Open-label; Pembrolizumab
ISSN (print) / ISBN
2072-6694
Journal
Cancers
Quellenangaben
Volume: 13,
Issue: 23,
Article Number: 6016
Publisher
MDPI
Publishing Place
St Alban-anlage 66, Ch-4052 Basel, Switzerland
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
CF Immunoanalytics (IMA)