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Updated: Jul 6, 2025
A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
Moving toward improved immune checkpoint immunotherapy for advanced prostate cancer
Marco A De Velasco1, Yurie Kura1, Kazutoshi Fujita2
1Department of Genome Biology, Kindai University Faculty of Medicine, Osakasayama, Japan.
Abstract:
Human prostate cancer is a heterogenous malignancy that responds poorly to immunotherapy targeting immune checkpoints. The immunosuppressive tumor microenvironment that is typical of human prostate cancer has been the main obstacle to these treatments. The effectiveness of these therapies is also hindered by acquired resistance, leading to slow progress in prostate cancer immunotherapy. Results from the highly anticipated late-stage clinical trials of PD-1/PD-L1 immune checkpoint blockade in patients with advanced prostate cancer have highlighted some of the obstacles to immunotherapy. Despite the setbacks, there is much that has been learned about the mechanisms that drive resistance, and new strategies are being developed and tested. Here, we review the status of immune checkpoint blockade and the immunosuppressive tumor microenvironment and discuss factors contributing to innate and adaptive resistance to immune checkpoint blockade within the context of prostate cancer. We then examine current strategies aiming to overcome these challenges as well as prospects.
Insights
Prostate cancer immunotherapy faces challenges from its immunosuppressive tumor microenvironment and resistance to PD-1/PD-L1 blockade. New strategies are being developed to overcome these obstacles for better treatment outcomes.
Area of Science:
- Oncology
- Immunology
- Cancer Research
Background:
- Human prostate cancer is a complex disease with a tumor microenvironment that suppresses the immune system.
- Current immunotherapies targeting immune checkpoints have shown limited efficacy in prostate cancer patients.
- Acquired resistance further complicates treatment effectiveness and hinders therapeutic progress.
Purpose of the Study:
- To review the current status of immune checkpoint blockade in prostate cancer.
- To discuss the role of the immunosuppressive tumor microenvironment in treatment failure.
- To examine factors contributing to resistance and explore novel therapeutic strategies.
Main Methods:
- Literature review of clinical trials and preclinical studies.
- Analysis of mechanisms underlying innate and adaptive resistance.
- Discussion of emerging strategies to overcome immunotherapy challenges.
Main Results:
- Late-stage clinical trials of PD-1/PD-L1 blockade revealed significant obstacles in advanced prostate cancer.
- The immunosuppressive tumor microenvironment is a key factor limiting immunotherapy effectiveness.
- Understanding resistance mechanisms is crucial for developing improved treatment approaches.
Conclusions:
- Prostate cancer immunotherapy, particularly immune checkpoint blockade, requires strategies to overcome the immunosuppressive tumor microenvironment and resistance.
- Ongoing research focuses on novel approaches to enhance patient response and improve outcomes.
- Further investigation into resistance mechanisms and combination therapies holds promise for future treatments.
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