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Cancers
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The Evolving Landscape of Tumor Microenvironment in Kidney and Bladder...
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The Evolving Landscape of Tumor Microenvironment in Kidney and Bladder Cancers

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

Deadline for manuscript submissions: closed (10 June 2022) | Viewed by 9887

Special Issue Editor

Dr. David D'Andrea

E-Mail Website
Guest Editor
Medical University of Vienna
Interests: urology; oncology; bladder cancer immunotherapy

Special Issue Information

Dear Colleagues,

Molecular discoveries of the interaction of the immune system with autologous tumors cells have allowed the development of immunomodulators which act on the immune checkpoints CTLA-4 and PD1 or PDL1. These monoclonal antibodies are one of the major advances in cancer treatment of the past decade and have already found widespread use in clinical routine. However, molecular and pathological tumor heterogeneity as well as host immune status influence therapy response and durability. One of the major challenges is to identify patients who are more likely to have a sustainable response to therapy. Unfortunately, we have not been able to identify any predictive biomarker to date. There is an unmet need for a better understanding of the tumor microenvironment to identify key pathways for immune resistance.

The aim of this Special Issue is to provide new insights of the tumor microenvironment in kidney and bladder cancers and its association with response to immunotherapy. A particular focus will be on translational implications for therapy selection, sequencing, and duration. This will include exploration of prognostic models, candidate biomarkers, therapeutic targets, and mechanisms of immune resistance.

Dr. David D'Andrea
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 short 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

  • immunotherapy
  • drug resistance
  • biomarkers
  • therapy sequencing
  • tumor microenvironment
  • kidney cancer
  • bladder cancer

Published Papers (3 papers)

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Research

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13 pages, 1991 KiB  
Article
IFN-Gamma Expression in the Tumor Microenvironment and CD8-Positive Tumor-Infiltrating Lymphocytes as Prognostic Markers in Urothelial Cancer Patients Receiving Pembrolizumab
by Toru Sakatani, Yuki Kita, Masakazu Fujimoto, Takeshi Sano, Akihiro Hamada, Kenji Nakamura, Hideaki Takada, Takayuki Goto, Atsuro Sawada, Shusuke Akamatsu and Takashi Kobayashi
Cancers 2022, 14(2), 263; https://doi.org/10.3390/cancers14020263 - 6 Jan 2022
Cited by 13 | Viewed by 2142
Abstract
Although immune checkpoint inhibitors have shown benefit for advanced urothelial carcinoma (aUC) patients, prognostication of treatment efficacy and response duration remains a clinical challenge. We evaluated the expression of immune markers in the tumor microenvironment and assessed their associations with response to and [...] Read more.
Although immune checkpoint inhibitors have shown benefit for advanced urothelial carcinoma (aUC) patients, prognostication of treatment efficacy and response duration remains a clinical challenge. We evaluated the expression of immune markers in the tumor microenvironment and assessed their associations with response to and survival after pembrolizumab treatment in 26 aUC patients. High levels of CD8+ tumor-infiltrating lymphocytes (TILs) were associated with favorable objective responses (23.0% vs. 15.3%, p = 0.0425), progression-free survival (median, 8.8 vs 2.1 months; hazard ratio (HR), 0.24; 95% confidence interval (CI), 0.07–0.66, p = 0.0060), and overall survival (median, >24.0 vs. 5.3 months; HR, 0.17; 95% CI, 0.04–0.56, p = 0.0034) compared with low levels. High interferon-gamma (IFNγ) expression levels were associated with longer post-progression survival (median, 4.9 vs. 1.0 months; HR, 0.18; 95% CI, 0.04–0.59, p = 0.0027) compared with low expression. Multivariate analysis incorporating clinical prognosticators demonstrated that the coincidence of low CD8+ T cells/IFNγ was an independent factor for unfavorable overall survival after pembrolizumab treatment (HR, 4.07; 95% CI, 1.36–12.73; p = 0.0125). The combination of low CD8+ TILs and IFNγ expression was an independent prognostic factor with predictive ability equivalent to previously reported clinical prognosticators. Full article
(This article belongs to the Special Issue The Evolving Landscape of Tumor Microenvironment in Kidney and Bladder Cancers)
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Review

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14 pages, 1520 KiB  
Review
Front-Line Therapy for Metastatic Renal Cell Carcinoma: A Perspective on the Current Algorithm and Future Directions
by Ameish Govindarajan, Daniela V. Castro, Zeynep B. Zengin, Sabrina K. Salgia, Jalen Patel and Sumanta K. Pal
Cancers 2022, 14(9), 2049; https://doi.org/10.3390/cancers14092049 - 19 Apr 2022
Cited by 4 | Viewed by 5060
Abstract
Over the last decade, the treatment paradigm of metastatic renal cell carcinoma has rapidly evolved, with notable changes in the front-line setting. Combination therapies involving the use of either doublet therapy with immune checkpoint inhibitors or combination VEGFR-directed therapies with immune checkpoint inhibitors [...] Read more.
Over the last decade, the treatment paradigm of metastatic renal cell carcinoma has rapidly evolved, with notable changes in the front-line setting. Combination therapies involving the use of either doublet therapy with immune checkpoint inhibitors or combination VEGFR-directed therapies with immune checkpoint inhibitors have significantly improved clinical outcomes, including prolonged overall survival and durable response to treatment. We aim to highlight the Food and Drug Administration-approved front-line therapy options, the navigation of treatment selection, and the future directions of metastatic renal cell carcinoma therapies. Full article
(This article belongs to the Special Issue The Evolving Landscape of Tumor Microenvironment in Kidney and Bladder Cancers)
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Other

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14 pages, 3512 KiB  
Systematic Review
Differential Prognosis and Response of Denovo vs. Secondary Muscle-Invasive Bladder Cancer: An Updated Systematic Review and Meta-Analysis
by Mario Pones, David D’Andrea, Keiichiro Mori, Mohammad Abufraj, Marco Moschini, Eva Comperat and Shahrokh F. Shariat
Cancers 2021, 13(10), 2496; https://doi.org/10.3390/cancers13102496 - 20 May 2021
Cited by 9 | Viewed by 2051
Abstract
To evaluate oncological outcomes of primary versus secondary muscle-invasive bladder cancer treated with radical cystectomy. Medline, Embase, Scopus and Cochrane Library were searched for eligible studies. Hazard ratios for overall survival (OS), cancer specific survival (CSS) and progression free survival (PFS) were calculated [...] Read more.
To evaluate oncological outcomes of primary versus secondary muscle-invasive bladder cancer treated with radical cystectomy. Medline, Embase, Scopus and Cochrane Library were searched for eligible studies. Hazard ratios for overall survival (OS), cancer specific survival (CSS) and progression free survival (PFS) were calculated using survival data extracted from Kaplan-Meier curves. A total of 16 studies with 5270 patients were included. Pooled analysis showed similar 5-year and 10-year OS (HR 1, p = 0.96 and HR 1, p = 0.14) and CSS (HR 1.02, p = 0.85 and HR 0.99, p = 0.93) between primMIBC and secMIBC. Subgroup analyses according to starting point of follow-up and second-look transurethral resection revealed similar results. Subgroup analyses of studies in which neoadjuvant chemotherapy was administered demonstrated significantly worse 5-year CSS (HR 1.5, p = 0.04) but not 10-year CSS (HR 1.36, p = 0.13) in patients with secMIBC. Patients with secMIBC had significantly worse PFS at 5-year (HR 1.41, p = 0.002) but not at 10-year follow-up (HR 1.25, p = 0.34). This review found comparable oncologic outcomes between primMIBC and secMIBC patients treated with RC regarding OS and CSS. Subgroup analysis showed worse 5-year CSS but not 10-year CSS for neoadjuvant chemotherapy in the secMIBC group. Prospective clinical trials incorporating molecular markers, that allow precise risk stratification of secMIBC and further research uncovering underlying molecular and clinical drivers of the heterogeneous group of secMIBC is needed. Full article
(This article belongs to the Special Issue The Evolving Landscape of Tumor Microenvironment in Kidney and Bladder Cancers)
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