Current Status and Future Perspectives of Immunotherapy for Locally Advanced or Metastatic Urothelial Carcinoma: A Comprehensive Review

Kim, Tae Jin; Koo, Kyo Chul

doi:10.3390/cancers12010192

Cited by 33 publications

(21 citation statements)

References 109 publications

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“…PD-1/PD-L1 inhibitors are antibodies that block either of these two molecules, cancelling the checkpoint activity and thus resulting in T cell activation [46]. They were first introduced as second-line therapy in BC treatment, but are slowly establishing themselves as first-line therapy [47]. There are currently three PD-L1 inhibitors and two PD-1 inhibitors approved by the FDA (Food and Drug Administration) for BC treatment (Table 1).…”

Section: Pd-1/pd-l1mentioning

confidence: 99%

Immunotherapy in Bladder Cancer: Current Methods and Future Perspectives

Wołącewicz

Hrynkiewicz

Grywalska

et al. 2020

Cancers

180

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Bladder cancer is one of the most significant genitourinary cancer, causing high morbidity and mortality in a great number of patients. Over the years, various treatment methods for this type of cancer have been developed. The most common is the highly efficient method using Bacillus Calmette-Guerin, giving a successful effect in a high percentage of patients. However, due to the genetic instability of bladder cancer, together with individual needs of patients, the search for different therapy methods is ongoing. Immune checkpoints are cell surface molecules influencing the immune response and decreasing the strength of the immune response. Among those checkpoints, the PD-1 (programmed cell death protein-1)/PD-L1 (programmed cell death protein ligand 1) inhibitors aim at blocking those molecules, which results in T cell activation, and in bladder cancer the use of Atezolizumab, Avelumab, Durvalumab, Nivolumab, and Pembrolizumab has been described. The inhibition of another pivotal immune checkpoint, CTLA-4 (cytotoxic T cell antigen), may result in the mobilization of the immune system against bladder cancer and, among anti-CTLA-4 antibodies, the use of Ipilimumab and Tremelimumab has been discussed. Moreover, several different approaches to successful bladder cancer treatment exists, such as the use of ganciclovir and mTOR (mammalian target of rapamycin) kinase inhibitors, IL-12 (interleukin-12) and COX-2 (cyclooxygenase-2). The use of gene therapies and the disruption of different signaling pathways are currently being investigated. Research suggests that the combination of several methods increases treatment efficiency and the positive outcome in individual.

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Section: Pd-1/pd-l1mentioning

confidence: 99%

Immunotherapy in Bladder Cancer: Current Methods and Future Perspectives

Wołącewicz

Hrynkiewicz

Grywalska

et al. 2020

Cancers

180

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“…The tumor types (urothelial carcinoma: sample 1. Clear cell renal cell carcinoma: samples 2 and 3) are currently approved 26 for anti-PD-L1 treatment or there are Phase III clinical studies showing evidence of benefit for the therapy 27 . These tumors were pathological grade 3 (sample 2) or 4 (samples 1 and 3) as evaluated from the hematoxylin and eosin staining (Figure 1a).…”

Section: Oncolytic Adenovirus-mediated Tumor Cell Lysis In Patient-dementioning

confidence: 99%

Tumor microenvironment remodeling by an engineered oncolytic adenovirus results in improved outcome from PD-L1 inhibition

et al. 2020

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Checkpoint inhibitors have revolutionized cancer therapy and validated immunotherapy as an approach. Unfortunately, responses are seen in a minority of patients. Our objective is to use engineered adenoviruses designed to increase lymphocyte trafficking and cytokine production at the tumor, to assess if they increase the response rate to checkpoint inhibition, as these features have been regarded as predictive for the responses. When Ad5/3-E2F-d24-hTNFa-IRES-hIL2 (an oncolytic adenovirus coding for TNFa and IL-2, also known as TILT-123) and checkpoint inhibitors were used together in fresh urological tumor histocultures, a significant shift toward immune activity (not only tumor necrosis alpha and interleukin-2 but also interferon gamma and granzyme B) and increased T-cell trafficking signals (CXCL10) was observed. In vivo, our viruses enabled an anti-PD-L1 (a checkpoint inhibitor) delivering complete responses in all the treated animals (hazard ratios versus anti-PD-L1 alone 0.057 [0.007; 0.451] or virotherapy alone 0.067 [0.011; 0.415]). To conclude, when an engineered oncolytic adenovirus was utilized to modify the tumor microenvironment towards what meta-analyses have pointed as predictive markers for checkpoint inhibitory therapy, the response to them increased synergistically. Of note, key findings were confirmed in fresh patient-derived tumor explants.

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“…The 5-year overall survival probability of 60% is dramatically reduced to less than 10% in case of early metastatic dissemination [23]. Currently, curative therapy options are missing and only a minority of patients with metastatic BLCa show long-term response to palliative treatments [24].…”

Section: Introduction: the Clinical Problem Of Bladder Cancermentioning

confidence: 99%

Evolution of Urothelial Bladder Cancer in the Context of Molecular Classifications

Minoli

Kiener

Thalmann

et al. 2020

IJMS

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Bladder cancer is a heterogeneous disease that is not depicted by current classification systems. It was originally classified into non-muscle invasive and muscle invasive. However, clinically and genetically variable tumors are summarized within both classes. A definition of three groups may better account for the divergence in prognosis and probably also choice of treatment. The first group represents mostly non-invasive tumors that reoccur but do not progress. Contrarily, the second group represent non-muscle invasive tumors that likely progress to the third group, the muscle invasive tumors. High throughput tumor profiling improved our understanding of the biology of bladder cancer. It allows the identification of molecular subtypes, at least three for non-muscle invasive bladder cancer (Class I, Class II and Class III) and six for muscle-invasive bladder cancer (luminal papillary, luminal non-specified, luminal unstable, stroma-rich, basal/squamous and neuroendocrine-like) with distinct clinical and molecular phenotypes. Molecular subtypes can be potentially used to predict the response to treatment (e.g., neoadjuvant chemotherapy and immune checkpoint inhibitors). Moreover, they may allow to characterize the evolution of bladder cancer through different pathways. However, to move towards precision medicine, the understanding of the biological meaning of these molecular subtypes and differences in the composition of cell subpopulations will be mandatory.

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Current Status and Future Perspectives of Immunotherapy for Locally Advanced or Metastatic Urothelial Carcinoma: A Comprehensive Review

Cited by 33 publications

References 109 publications

Immunotherapy in Bladder Cancer: Current Methods and Future Perspectives

Immunotherapy in Bladder Cancer: Current Methods and Future Perspectives

Tumor microenvironment remodeling by an engineered oncolytic adenovirus results in improved outcome from PD-L1 inhibition

Evolution of Urothelial Bladder Cancer in the Context of Molecular Classifications

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