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Current Status and Future Directions of Immuncheckpoint Inhibitors for the...
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Current Status and Future Directions of Immuncheckpoint Inhibitors for the Treatment of Urologic Cancers

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Therapy".

Deadline for manuscript submissions: closed (15 September 2021) | Viewed by 9883

Special Issue Editor

Dr. Sonia Vallet

E-Mail Website
Guest Editor
Division of Internal Medicine II, University Hospital Krems, Karl Landsteiner University of Health Sciences, 3500 Krems, Austria
Interests: supportive care in cancer; bone metastases; side effects of immune checkpoint inhibitors; multiple myeloma; advanced bladder cancer; metastatic kidney cancer; metastatic prostate cancer
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear colleagues,

Immune-checkpoint inhibitors (ICI) have become a cornerstone in the treatment armamentarium for patients with urothelial and renal cell carcinoma.

In metastatic urothelial cancer, PD-1 and PD-L1 inhibitors represent an effective second-line treatment option and offer a valid alternative to chemotherapy in the first line setting for cisplatin-ineligible patients. More recently, the PD-1 inhibitor pembrolizumab has also been approved for Bacillus Calmette–Guerin (BCG)-unresponsive, high-risk non-muscle invasive bladder cancer.

In addition to the PD-1 inhibitor nivolumab in patients progressing on anti-angiogenesis agents, current standard immunotherapy for advanced treatment-naïve kidney cancer includes a CTLA-4 blockade with ipilimumab, as well as combinations of the tyrosine-kinase inhibitor axitinib with either pembrolizumab or the PD-L1 antagonist avelumab.

Clinical trials are currently investigating the interplay of ICI with chemotherapy, hormone antagonists, and novel targeted agents, as well as surgical procedures. Research efforts are also directed to potentiating the response in prostate cancers and germ cell tumors and to identifying predictive biomarkers for optimal patient selection.

This Special Issue aims at covering the recent advances and future challenges of ICI-based strategies in urologic cancers, original and review articles are welcomed.

Dr. Sonia Vallet
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • immuncheckpoint inhibitors
  • kidney cancer
  • bladder cancer
  • prostate cancer

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Published Papers (3 papers)

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Research

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13 pages, 431 KiB  
Article
Efficacy and Safety of Checkpoint Inhibitor Treatment in Patients with Advanced Renal or Urothelial Cell Carcinoma and Concomitant Chronic Kidney Disease: A Retrospective Cohort Study
by Florian Seydel, Susanne Delecluse, Martin Zeier, Tim Holland-Letz, Georg Martin Haag, Anne Katrin Berger, Barbara Christine Grün, Nina Bougatf, Markus Hohenfellner, Stefan Duensing, Dirk Jäger and Stefanie Zschäbitz
Cancers 2021, 13(7), 1623; https://doi.org/10.3390/cancers13071623 - 1 Apr 2021
Cited by 5 | Viewed by 2137
Abstract
Background: Checkpoint inhibitors are a standard of care in the treatment of advanced renal cell carcinoma (RCC) and urothelial carcinoma (UC). Patients with these tumors often suffer from concomitant chronic kidney disease (CKD). Limited data are available on the efficacy and toxicity [...] Read more.
Background: Checkpoint inhibitors are a standard of care in the treatment of advanced renal cell carcinoma (RCC) and urothelial carcinoma (UC). Patients with these tumors often suffer from concomitant chronic kidney disease (CKD). Limited data are available on the efficacy and toxicity of checkpoint inhibitors in patients with CKD. Methods: We retrospectively analyzed 126 patients who received checkpoint inhibitors for RCC (n = 85) or UC (n = 41) and analyzed the frequency of treatment- and immune-related adverse events (AEs). We performed a multivariate analysis to determine progression-free survival (PFS) and overall survival (OS). Results: A total of 38.9% of patients had CKD. Frequencies of general AEs (49.0% in CKD vs. 48.1%, p > 0.99999) and immune-related AEs (28.6 vs. 24.7%, p ≥ 0.9999) did not significantly differ between the groups. There was no difference in PFS for patients with RCC or UC and CKD or without CKD (RCC: 6.81 vs. 7.54 months, HR 1.000 (95%CI 0.548–01.822), p = 0.999; UC:2.33 vs. 3.67 months, HR 01.492 (95%CI 0.686–3.247), p = 0.431). CKD appeared to be a potential effect modifier for OS in both RCC and UC (RCC: NR vs. 23.9 months, HR 0.502 (95%CI 0.219–1.152), p = 0.104; UC:18.84 vs. 15.42 months, HR 0.656 (95%CI 0.296–1.454), p = 0.299). Conclusions: Checkpoint inhibitor treatment in our cohort of patients with CKD was as safe and efficient as in the cohort of patients without CKD. Full article
(This article belongs to the Special Issue Current Status and Future Directions of Immuncheckpoint Inhibitors for the Treatment of Urologic Cancers)
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Review

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22 pages, 1749 KiB  
Review
Checkpoint Inhibition in Bladder Cancer: Clinical Expectations, Current Evidence, and Proposal of Future Strategies Based on a Tumor-Specific Immunobiological Approach
by Mariangela Mancini, Marialaura Righetto and Elfriede Noessner
Cancers 2021, 13(23), 6016; https://doi.org/10.3390/cancers13236016 - 29 Nov 2021
Cited by 24 | Viewed by 3187
Abstract
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) [...] Read more.
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. Full article
(This article belongs to the Special Issue Current Status and Future Directions of Immuncheckpoint Inhibitors for the Treatment of Urologic Cancers)
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22 pages, 1289 KiB  
Review
Prognostic and Predictive Value of Tumor-Infiltrating Immune Cells in Urothelial Cancer of the Bladder
by Sandra van Wilpe, Eveline C. F. Gerretsen, Antoine G. van der Heijden, I. Jolanda M. de Vries, Winald R. Gerritsen and Niven Mehra
Cancers 2020, 12(9), 2692; https://doi.org/10.3390/cancers12092692 - 21 Sep 2020
Cited by 29 | Viewed by 3924
Abstract
The prognosis and responsiveness to chemotherapy and checkpoint inhibitors differs substantially among patients with bladder cancer (BC). There is an unmet need for biomarkers that can accurately predict prognosis and treatment outcome. Here, we describe the available literature on the prognostic and predictive [...] Read more.
The prognosis and responsiveness to chemotherapy and checkpoint inhibitors differs substantially among patients with bladder cancer (BC). There is an unmet need for biomarkers that can accurately predict prognosis and treatment outcome. Here, we describe the available literature on the prognostic and predictive value of tumor-infiltrating immune cells in BC. Current evidence indicates that a high density of tumor-infiltrating CD8+ T cells is a favorable prognostic factor, whereas PD-L1 expression and tumor-associated macrophages are unfavorable prognostic features. While PD-L1 expression appears unsuccessful as a biomarker for the response to checkpoint inhibitors, there are some indications that high CD8+ T cell infiltration, low transforming growth factor-beta signaling and low densities of myeloid-derived suppressor cells are associated with response. Future studies should focus on combinations of biomarkers to accurately predict survival and response to treatment. Full article
(This article belongs to the Special Issue Current Status and Future Directions of Immuncheckpoint Inhibitors for the Treatment of Urologic Cancers)
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