The impact of preoperative immune checkpoint inhibitors on kidney and bladder cancer surgeries: a systematic review☆

2021 ◽  
pp. 100765
Author(s):  
Aline Petracco Petzold ◽  
Fernanda Nascimento Lubianca ◽  
Laura Gazal Passos ◽  
Carolina Knorst Keppler ◽  
Nicole Bernd Becker ◽  
...  
Keyword(s):  
Systematic Review ◽  
Bladder Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
The Impact

RNF43 mutations to predict survival from treatment with immune checkpoint inhibitors and are associated with a high tumor mutation burden in bladder cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16528-e16528
Author(s):  
Liping Li ◽  
Mengmei Yang ◽  
Mengli Huang
Keyword(s):  
Bladder Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Negative Regulator ◽  
Wilcoxon Test ◽  
Wild Type ◽  
Tumor Mutation Burden ◽  
Mutation Burden ◽  
The Impact

e16528 Background: Immune checkpoint inhibitors (ICIs) targeting PD-1/L1 have been approved as first-line treatment for cisplatin-ineligible patients and as second-line therapy for patients with metastatic urothelial carcinoma of the bladder. Biomarkers can help select patients who are more likely to response to ICIs. RNF43 is an E3 ubiquitin ligase that acts as a negative regulator of Wnt/β-catenin signaling pathway. In colorectal cancer (CRC) patients treated with immune checkpoint inhibitors (ICIs), RNF43 mutations predicted longer overall survival (OS). The impact of RNF43 mutations on the efficiency of ICIs in bladder cancer(BLC) remains to be explored. Methods: We downloaded the mutation and clinical data of 211 BLC patients treated with ICIs from the immunotherapeutic cohort published by Samstein et al. (2019). OS analyses were conducted using Kaplan-Meier curves and log-rank tests. Wilcoxon test was used for the comparison of TMB. We also downloaded a TCGA cohort for prognostic analysis. The correlations between RNF43 and immune infiltrates were analyzed in the TIMER2.0 database. Statistical significance was set at p = 0.05. Results: RNF43 mutations were identified in 4.3%(9/211) and 3%(13/438) BLC patients in the immunotherapeutic and TCGA cohort, respectively. In the immunotherapeutic cohort, patients with RNF43 mutations had significantly longer OS (25 months vs 8 months; p = 0.015) and higher tumor mutation burden(TMB, 42.3 vs 7.9; p = 3.15E-06) than RNF43-wild-type patients. Different from this, no significant difference was found in OS between RNF43-mutant and RNF43-wild-type BLC patients with standard treatment in the TCGA cohort (p = 0.696). These results indicated that RNF43 was not a prognostic factor but a predictive biomarker of survival in BLC treated with ICIs. No difference was observed in subsets of immune cells between RNF43-mutant and the RNF43-wide-type BLC patients, including neutrophils, macrophages, CD8+ T cells, Tregs, B cells and NK cells. Conclusions: RNF43 mutations may be a predictor of survival benefit from ICIs in bladder cancer and correlated with higher TMB. Further studies in other ICI-treated cohorts are needed to confirm these results.

scholarly journals The impact of smoking on the effectiveness of immune checkpoint inhibitors — a systematic review and meta-analysis

2019 ◽  
Vol 59 (1) ◽  
pp. 96-100 ◽  
Author(s):  
Kirsty Wai Chung Lee ◽  
Sarah J. Lord ◽  
Lawrence Kasherman ◽  
Ian Marschner ◽  
Martin Stockler ◽  
...  
Keyword(s):  
Systematic Review ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Meta Analysis ◽  
The Impact

scholarly journals Strategies to Improve Cancer Immune Checkpoint Inhibitors Efficacy, Other Than Abscopal Effect: A Systematic Review

Cancers ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 539 ◽  
Author(s):  
Vito Longo ◽  
Oronzo Brunetti ◽  
Amalia Azzariti ◽  
Domenico Galetta ◽  
Patrizia Nardulli ◽  
...  
Keyword(s):  
Systematic Review ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Response Rate ◽  
Checkpoint Inhibitors ◽  
Research Field ◽  
Oncolytic Viruses ◽  
Abscopal Effect ◽  
Tumor Mutational Burden ◽  
The Impact

Despite that the impact of immune checkpoint inhibitors on malignancies treatment is unprecedented, a lack of response to these molecules is observed in several cases. Differently from melanoma and non-small cell lung cancer, where the use of immune checkpoint inhibitors results in a high efficacy, the response rate in other tumors, such as gastrointestinal cancers, breast cancer, sarcomas, and part of genitourinary cancers remains low. The first strategy evaluated to improve the response rate to immune checkpoint inhibitors is the use of predictive factors for the response such as PD-L1 expression, tumor mutational burden, and clinical features. In addition to the identification of the patients with a higher expression of immune checkpoint molecules, another approach currently under intensive investigation is the use of therapeutics in a combinatory manner with immune checkpoint inhibitors in order to obtain an enhancement of efficacy through the modification of the tumor immune microenvironment. In addition to the abscopal effect induced by radiotherapy, a lot of studies are evaluating several drugs able to improve the response rate to immune checkpoint inhibitors, including microbiota modifiers, drugs targeting co-inhibitory receptors, anti-angiogenic therapeutics, small molecules, and oncolytic viruses. In view of the rapid and extensive development of this research field, we conducted a systematic review of the literature identifying which of these drugs are closer to achieving validation in the clinical practice.

scholarly journals Strategies to Improve Cancer Immune Checkpoint Inhibitors Efficacy, other than Abscopal Effect: A Systematic Review

2019 ◽  
Author(s):  
Vito Longo ◽  
oronzo Brunetti ◽  
Amalia Azzariti ◽  
Domenico Galetta ◽  
Patrizia Nardulli ◽  
...  
Keyword(s):  
Systematic Review ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Response Rate ◽  
Checkpoint Inhibitors ◽  
Research Field ◽  
Oncolytic Viruses ◽  
Abscopal Effect ◽  
Improve Response Rate ◽  
The Impact

Despite the impact of immune checkpoint inhibitors on malignancies treatment is unprecedented, a lack of response to these molecules is observed in several cases. Differently from melanoma and non-small cell lung cancer, where the use of immune checkpoint inhibitors results in a high efficacy, the response rate in other tumors, such as gastrointestinal cancers, breast cancer, sarcomas, and part of genitor-urinary cancers remains low. The first strategy evaluated to improve the response rate to immune checkpoint inhibitors is the use of predictive factors for the response as PD-L1 expression, tumor mutational burden, and clinical features. In addition to the identification of the patients with a high sensibility to immune checkpoint inhibitors, another approach currently under intensive investigation is the use of therapeutics in a combinatory manner with immune checkpoint inhibitors to obtain an enhancement of efficacy through the modification of the tumor immune microenvironment. In addition to the abscopal effect induced by radiotherapy, a lot of studies are evaluating several drugs able to improve response rate to immune checkpoint inhibitors, including microbiota modifiers, drugs targeting co-inhibitors receptors, anti-angiogenic therapeutics, small molecules, and oncolytic viruses. In view of the rapid and extensive development of this research field, we conducted a systematic review of the literature identifying which of these drugs are closer to achieving validation in the clinical practice.

scholarly journals The Impact of Immune Checkpoint-Inhibitors Therapy in Urinary Bladder Cancer

Onco ◽  
2021 ◽  
Vol 1 (1) ◽  
pp. 3-22
Author(s):  
Ana Lúcia Silva ◽  
Pedro Abreu-Mendes ◽  
Diana Martins ◽  
Fernando Mendes
Keyword(s):  
Bladder Cancer ◽  
Cell Death ◽  
Tumor Microenvironment ◽  
Programmed Cell Death ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Cytotoxic T Cells ◽  
The Impact ◽  
Cell Death Protein

Bladder cancer (BC) is one of the most common cancers in the world. From an early age, it was observed that chronic inflammation is associated with conditions favorable to the development of tumors, as well as the tumor microenvironment. Moreover, regulating tumor progression also interferes with the therapy’s response. The interaction between the tumor and the immune system led to the development of new immune therapies, the immune checkpoint inhibitors. Immunotherapy has shown a better safety profile, survival, and tolerance compared to standard chemotherapy. This therapy offers an effective alternative to patients who are ineligible for cisplatin and patients with advanced disease progression after platinum-based therapy. The first immunotherapy approved for BC was intravesical instillation with Bacillus Calmette–Guérin, for tumors at early stages. Later, immunotherapy focused on immune checkpoint inhibitors, namely, anti-programmed cell death protein 1 (PD1), anti-programmed cell death protein ligand 1(PD-L1), and anti-antigen 4 associated with cytotoxic T cells (CTLA-4). Currently, five immune checkpoint inhibitors for advanced BC are approved by the Food and Drug Administration (FDA): Atezolizumab, Durvalumab, Avelumab, Pembrolizumab, and Nivolumab. This review addresses the correlation between inflammation, tumor microenvironment, and cancer; various studies regarding immune checkpoint inhibitors, either in monotherapy or in combination therapy, are also addressed.

scholarly journals Perioperative Systemic Treatment for Muscle-Invasive Bladder Cancer: Current Evidence and Future Perspectives

2021 ◽  
Vol 22 (13) ◽  
pp. 7201
Author(s):  
In-Ho Kim ◽  
Hyo-Jin Lee
Keyword(s):  
Bladder Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Systemic Treatment ◽  
Checkpoint Inhibitors ◽  
Invasive Bladder Cancer ◽  
Current Evidence ◽  
Future Perspectives ◽  
Muscle Invasive Bladder Cancer ◽  
Muscle Invasive

Radical cystectomy is the primary treatment for muscle-invasive bladder cancer; however, approximately 50% of patients develop metastatic disease within 2 years of diagnosis, which results in dismal prognosis. Therefore, systemic treatment is important to improve the prognosis of muscle-invasive bladder cancer. Currently, several guidelines recommend cisplatin-based neoadjuvant chemotherapy before radical cystectomy, and adjuvant chemotherapy is recommended in patients who have not received neoadjuvant chemotherapy. Immune checkpoint inhibitors have recently become the standard treatment option for metastatic urothelial carcinoma. Owing to their clinical benefits, several immune checkpoint inhibitors, with or without other agents (including other immunotherapy, cytotoxic chemotherapy, and emerging agents such as antibody drug conjugates), are being extensively investigated in perioperative settings. Several studies for perioperative immunotherapy have shown that immune checkpoint inhibitors have promising efficacy with relatively low toxicity, and have explored the predictive molecular biomarkers. Herein, we review the current evidence and discuss the future perspectives of perioperative systemic treatment for muscle-invasive bladder cancer.

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