New immunotherapies for high-risk non-muscle invasive bladder cancer: Current state and future perspectives

Cañizo, C. Gómez del; Jimenez, Marta; Vallejo, E. Peña; Ojeda, J.M. Duarte; Kehrman, F. de la Rosa; Antolín, Alfredo Rodríguez; Guerrero-Ramos, Félix

doi:10.1016/j.acuroe.2020.10.008

Cited by 2 publications

(1 citation statement)

References 34 publications

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“…The use of anti-programmed death ligand-1 (PD-L1) check point inhibitors is rising as a novel treatment in high risk NMIBC due to limited efficacy of Bacillus Calmette-Guérin (BCG) therapy 7 , where up to 50-70% of BCG-treated patients will experience a high-grade recurrence despite the instillations 8 . Despite promising preliminary results, the response to these drugs varies among patients 9,10 .…”

Section: Introductionmentioning

confidence: 99%

Comprehensive Landscape of Non-muscle Invasive Bladder Cancer Tumour Microenvironment and Prognostic value of Cancer-Associated Myofibroblasts

Cañizo,

Guerrero-Ramos,

Escavy

et al. 2023

Preprint

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Background: Non-muscle-invasive bladder cancer (NMIBC) is challenging due to high recurrence and progression rates. Bacillus Calmette-Guerin (BCG) is the standard treatment for high-risk NMIBC, but emergence of anti-PD-1/PD-L1 drugs necessitates a deeper understanding of the tumour microenvironment (TME) for improved prognostic markers and therapies. Objective: To extensively analyse NMIBC's TME, focusing on cellular composition, PD-L1 expression, and the role of cancer-associated fibroblasts (CAFs) in prognosis. Design, Setting, and Participants: A prospective study between December 2019 and December 2022 collected 98 NMIBC and non-pathological tissue (NPT) samples from cytology-positive/suspicious patients (66 patients in final analysis). Intervention(s): Assessment of immune and non-immune cell subsets and PD-L1 expression using flow cytometry. Transcriptomic data and histology validated findings and evaluated prognostic markers. Outcome Measurements and Statistical Analysis: We assessed the distribution of 11 cell types and PD-L1 expression in NMIBC, comparing them to NPT and across pathological stage and grade. Statistical methods evaluated the association of myofibroblasts (myoCAFs) and other CAF subsets with progression-free and recurrence-free survival. Results and Limitations: Compared to NPT, NMIBC's TME exhibited microvascular alterations, increased fibroblast and myoCAF presence, and varying immune cell distribution. Heterogeneous PD-L1 expression was observed across subsets, with cancer cells as primary potential anti-PD-L1 binding targets. MyoCAFs were associated with high grade tumours and poor prognosis, while other CAF subsets were not. Study limitations included a modest sample size and a relatively short follow-up period. Conclusions: This comprehensive analysis provides a roadmap to establish the full NMIBC's TME, highlighting myoCAFs as potential prognostic markers. Understanding its complexity may enhance therapeutic strategies and risk stratification for NMIBC patients. Further research is essential to validate findings and explore myoCAF implications in NMIBC therapy. Patient Summary: We described the composition of non-muscle invasive bladder cancer, identified cellular components associated with aggressive tumors, and found markers to predict outcome.

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Section: Introductionmentioning

confidence: 99%

Comprehensive Landscape of Non-muscle Invasive Bladder Cancer Tumour Microenvironment and Prognostic value of Cancer-Associated Myofibroblasts

Cañizo,

Guerrero-Ramos,

Escavy

et al. 2023

Preprint

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Novel Therapeutic Strategies for BCG-unresponsive Non-muscle Invasive Bladder Cancer

Zhang

Ding

2022

ann urol oncol

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Development of therapeutic strategies for non-muscle-invasive bladder cancer (NMIBC) that failed intravesical Bacillus Calmette - Guerin (BCG) therapy remains an urgent priority for clinicians. Currently, radical cystectomy is the recommended standard of care treatment options for these patients. Intravesical chemotherapy using gemcitabine and docetaxel are regarded as the most effective treatment options for unresponsive NMIBC, however, these options are ineffective in the control of bladder cancer. In this review, we present the definition of BCG unresponsive NMIBC and discuss about the recent management options that include immunotherapy, intravesical chemotherapy, gene therapy, and targeted individualized therapy. Notably, immunotherapy is the most recent strategy utilizing the PD-1/PD-L1 and other immune checkpoint inhibitors (ICIs). Pembrolizumab (KEYNOTE-057), Atezolizumab (SWOG S1605) and Nivolumab were developed and are efficacious in BCG –unresponsive NMIBC. In summary, ICIs are considered as the most promising agent for BCG unresponsive NMIBC in the future.

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New immunotherapies for high-risk non-muscle invasive bladder cancer: Current state and future perspectives

Cited by 2 publications

References 34 publications

Comprehensive Landscape of Non-muscle Invasive Bladder Cancer Tumour Microenvironment and Prognostic value of Cancer-Associated Myofibroblasts

Comprehensive Landscape of Non-muscle Invasive Bladder Cancer Tumour Microenvironment and Prognostic value of Cancer-Associated Myofibroblasts

Novel Therapeutic Strategies for BCG-unresponsive Non-muscle Invasive Bladder Cancer

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