Neoadjuvant Immunotherapy in Genitourinary Tumors

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

Deadline for manuscript submissions: closed (20 October 2024) | Viewed by 3291

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Department of Maternal-Child and Urological Sciences, Policlinico Umberto I Hospital, Sapienza University of Rome, 00161 Rome, Italy
Interests: urology; uro-oncology; andrology; kidney stones; urolithiasis; incontinence; CEUS; contrast-enhanced ultrasound; kidney cancer; bladder cancer; prostate cancer; penile cancer; reflux
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1. Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, Department of Biology, College of Science and Technology, Temple University, Philadelphia, PA 19122, USA
2. Department of Biomedical Sciences, Humanitas University, 20072 Pieve Emanuele, Italy
Interests: uro-oncology
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1. Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, Department of Biology, College of Science and Technology, Temple University, Philadelphia, PA 19122, USA
2. Department of Medical Biotechnology, University of Siena, 53100 Siena, Italy
Interests: cell cycle dependent kinase (CDK); retinoblastoma protein family; cancer therapy; mesothelioma; CDK9; Rb2
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Special Issue Information

Dear Colleagues,

Genitourinary (GU) malignancies affect many people worldwide, with millions of new cases diagnosed annually. In recent decades, our understanding of cancer and its pathophysiology has evolved. It has been well established that cancer cells have developed multiple mechanisms to avoid the immune system. 

The use of immunotherapy in the preoperative or neoadjuvant setting is supported by preclinical studies showing that stronger and broader immune responses can be generated when immunotherapy is administered with the primary tumor and/or regional lymph nodes intact. By interfering with pathways in the tumor microenvironment, immune checkpoint inhibitors (ICIs) allow the immune system to “ramp up” and effectively target malignant cells. 

This Special Issue delves into the role of immunotherapy in the treatment of GU malignancies, specifically urothelial, renal, prostate, and other rarer tumors. The goal is to enhance “precision therapy” evidence to increase overall survival and progression-free survival. 

Dr. Antonio Tufano
Dr. Nadia Cordua
Prof. Dr. Antonio Giordano
Guest Editors

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Keywords

  • immunotherapy
  • immune checkpoint inhibitor
  • bladder cancer
  • urothelial cancer
  • kidney cancer
  • renal cell carcinoma
  • prostate cancer
  • testicular cancer
  • penile cancer
  • adrenocortical carcinoma

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Published Papers (2 papers)

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Research

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16 pages, 2922 KiB  
Article
The Novel HDAC Inhibitor OBP-801 Promotes MHC Class I Presentation Through LMP2 Upregulation, Enhancing the PD-1-Targeting Therapy in Clear Cell Renal Cell Carcinoma
by Tsukasa Narukawa, Shusuke Yasuda, Mano Horinaka, Keiko Taniguchi, Takahiro Tsujikawa, Mie Morita, Osamu Ukimura and Toshiyuki Sakai
Cancers 2024, 16(23), 4058; https://doi.org/10.3390/cancers16234058 - 4 Dec 2024
Cited by 1 | Viewed by 1195
Abstract
Background: Histone deacetylase (HDAC) inhibitors have been reported to exhibit immunomodulatory activities, including the upregulation of major histocompatibility complex class I (MHC class I). Although the immunoproteasome plays a pivotal role in MHC class I antigen presentation, its effect on immunotherapy for clear [...] Read more.
Background: Histone deacetylase (HDAC) inhibitors have been reported to exhibit immunomodulatory activities, including the upregulation of major histocompatibility complex class I (MHC class I). Although the immunoproteasome plays a pivotal role in MHC class I antigen presentation, its effect on immunotherapy for clear cell renal cell carcinoma (ccRCC) remains unclear. Methods: This study assessed whether OBP-801, a novel HDAC inhibitor, affects the expression of immunoproteasome subunits and subsequently the MHC class-I-mediated anti-cancer immunity in ccRCC. We analyzed the data of 531 patients with ccRCC from the Cancer Genome Atlas Kidney Clear Cell Carcinoma database. We further evaluated the treatment efficacy of the combination of OBP-801 and anti-PD-1 in a ccRCC mouse model. Results: Low molecular mass polypeptide (LMP) 2 was correlated most positively with CD3E, CD8A, and CD8B expression and estimated CD8+ T cell number. In vitro studies showed that OBP-801 upregulated MHC class I presentation by inducing LMP2 expression in the ccRCC cell lines RENCA, 786-O, and Caki-1. In vivo studies in a syngeneic mouse model with subcutaneous implantation of RENCA cells showed that OBP-801 treatment increased the percentage of CD45+CD3e+ T cells in tumor-infiltrating lymphocytes. The combination of anti-PD-1 antibody and OBP-801 enhanced the anti-tumor effect, LMP2 protein expression, and MHC class I presentation in tumor cells. MHC class I presentation in the tumors of each mouse was positively correlated with the percentage of CD45+CD3e+ T cells. Conclusions: Our results demonstrate that OBP-801 promotes MHC class I presentation through LMP2 upregulation in tumor cells and thereby potentiates PD-1-targeting therapy. These data suggest that the combination of OBP-801 and anti-PD-1 treatment is a promising therapeutic strategy for ccRCC. Full article
(This article belongs to the Special Issue Neoadjuvant Immunotherapy in Genitourinary Tumors)
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Review

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28 pages, 794 KiB  
Review
Role of Neoadjuvant Immunotherapy in Genitourinary Malignancies
by Adam Khorasanchi, Karan Jatwani, Lingbin Meng, Katharine A. Collier, Debasish Sundi, Shawn Dason, Eric A. Singer, Dharmesh Gopalakrishnan, Amir Mortazavi, Gurkamal Chatta and Yuanquan Yang
Cancers 2024, 16(24), 4127; https://doi.org/10.3390/cancers16244127 - 10 Dec 2024
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Abstract
Genitourinary (GU) malignancies are common and associated with significant morbidity and mortality. In patients with localized GU cancers, surgical resection or definitive radiation remain the mainstays of treatment. Despite definitive treatment, many patients with high-risk localized disease experience recurrence. There is growing interest [...] Read more.
Genitourinary (GU) malignancies are common and associated with significant morbidity and mortality. In patients with localized GU cancers, surgical resection or definitive radiation remain the mainstays of treatment. Despite definitive treatment, many patients with high-risk localized disease experience recurrence. There is growing interest in using neoadjuvant immunotherapy to improve outcomes. This narrative review summarizes the current evidence for neoadjuvant immunotherapy in patients with localized high-risk GU cancers including renal cell carcinoma, urothelial carcinoma, prostate cancer, penile squamous cell carcinoma, and testicular germ cell tumors. We also discuss ongoing clinical trials and candidate biomarkers to optimize patient selection and improve treatment outcomes. Full article
(This article belongs to the Special Issue Neoadjuvant Immunotherapy in Genitourinary Tumors)
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