Immunotherapy for Prostate Cancer: How It Works and When It May Be Effective
Immunotherapy helps the immune system find and attack cancer cells throughout the body. While this approach is promising, it tends to be most effective when combined with treatments that first make the tumour more visible to the immune system.
This is largely because prostate tumours are considered “cold,” meaning they trigger little to no immune response. Without that existing activity, boosting the immune system has a limited effect on tumour growth.
Because of this, doctors rarely use immunotherapy alone for prostate cancer. Instead, an immune response usually needs to be generated so that immunotherapy has something to amplify.
This guide explains how immunotherapy works in prostate cancer, its limitations, and how it fits into broader treatment options.
Key Points
- Immunotherapy helps the immune system attack cancer cells, but in prostate cancer it is often limited as a standalone treatment because tumours trigger little immune response.
- Most prostate tumours are “cold,” meaning there is not enough existing immune activity for immunotherapy to work on its own
- Treatments that improve tumour visibility, particularly those that release intact tumour antigens, can help create the immune response needed for immunotherapy to be effective
- Combining immunotherapy with non-thermal focal therapies may lead to a stronger and more targeted immune response beyond the primary tumour
What Is Immunotherapy in Prostate Cancer
Immunotherapy is a treatment approach that helps the immune system identify and destroy cancer cells. It works in part by enhancing the activity of T cells, a type of white blood cell responsible for recognizing and attacking abnormal cells in the body.
In simple terms, T cells act as the immune system’s surveillance mechanism. When they recognize a cancer cell, they can bind to it and trigger its destruction. However, cancer cells can develop ways to avoid detection or suppress this response, allowing them to grow unchecked.
Immunotherapy is designed to overcome these barriers by enhancing T-cell activity or removing the signals that prevent them from attacking cancer cells. In prostate cancer, this process is more complex, as the immune system often does not strongly recognize the tumour to begin with.
Current Immunotherapy Options in Prostate Cancer
Because immunotherapy can act at different points in the immune response, there are several ways it can be applied. Some approaches aim to stimulate immune recognition, while others remove the signals that prevent immune cells from acting.
In prostate cancer, only a limited number of these approaches are used in clinical practice.
Checkpoint Inhibitors
Checkpoint inhibitors are one of the main classes of immunotherapy used in prostate cancer. These drugs work by removing signals that block T cells from attacking cancer cells, allowing the immune system to respond more effectively.
Common examples include pembrolizumab, dostarlimab, and ipilimumab. These treatments are typically given through intravenous infusion every few weeks.
In standard clinical settings, their use is often limited to patients with specific tumour characteristics, such as certain genetic markers. However, when combined with treatments that improve how the tumour is recognised by the immune system, their role may extend beyond these cases.
Prostate Cancer Vaccine
Sipuleucel-T is a therapeutic cancer vaccine designed to train a patient’s own immune cells to recognise prostate cancer. It is used in advanced prostate cancer cases where the disease has progressed despite hormone therapy. While it can help stimulate an immune response, its role is limited and it is not typically used with curative intent.
Emerging Immunotherapies
Newer approaches are being developed to improve how immunotherapy works in prostate cancer. These include targeted T-cell therapies and bispecific antibodies designed to bring immune cells into closer contact with cancer cells. Early clinical trials have shown promising results, including reductions in PSA levels in some patients.
Why Immunotherapy Alone Often Has Limited Results
Despite these developments, immunotherapy is not typically used as a standalone treatment in prostate cancer. While it is a promising approach, its effectiveness is largely limited by tumour biology.
This is because immunotherapy, including immune checkpoint inhibitors, relies on existing immune activity that can be amplified. As an immunologically cold tumour, prostate cancer has low immune activity and fewer active T cells, meaning there is often little for immunotherapy to act on.
What Needs to Change for Immunotherapy to Work in Prostate Cancer
For immunotherapy to work, prostate cancer must first shift from a cold tumour to a hot tumour (also known as a T-cell-inflamed tumour). One way to do this is by inducing immunogenic cell death (ICD).
The goal of ICD is to kill a subset of cancer cells in a way that releases tumour antigens, allowing the immune system to better identify cancer cells throughout the body and trigger a broader immune response, sometimes referred to as the abscopal effect.
There are several treatment approaches that can trigger an abscopal effect:
- Oncolytic Viruses: Recombinantly engineered viruses injected directly into tumours to cause cell lysis and release neoantigens.
- Traditional Therapies: Radiation therapy and some forms of chemotherapy can damage tumour DNA, activate the cGAS-STING pathway, and help prime immune cells.
- Ablation Therapies: Focal ablation techniques can destroy cancer cells while releasing tumour antigens and other signalling molecules that attract immune cells.
While all three approaches can trigger an immune response, they do not affect tumour recognition in the same way. Some methods damage or degrade tumour antigens during treatment, limiting how clearly the immune system can identify cancer cells.
Because of this, the way tumour cells are destroyed directly influences whether immunotherapy can work. Approaches that preserve tumour structure and release intact antigens are more likely to support immune recognition, while those that disrupt these signals can reduce the effectiveness of treatment.
Thermal Treatments and Antigen Destruction
Some of the most common prostate cancer ablation therapies are thermal treatments, including high-intensity focused ultrasound (HIFU) and cryotherapy.
While these approaches can be effective for removing targeted tumour tissue, the extreme temperatures involved in treatment can denature tumour proteins, reducing the availability of intact prostate-specific tumour antigens and limiting the treatment’s ability to trigger an abscopal effect.
As a result, although the primary tumour may be treated successfully, the resulting immune response is often weaker, reducing the potential for immunotherapy to build on that response.
Non-Thermal Approaches and Antigen Preservation
Unlike treatments that rely on extreme heat or freezing, non-thermal focal therapies destroy cancer cells while allowing tumour antigens to remain intact and be released into surrounding tissue, increasing the likelihood of triggering an abscopal effect.
These non-thermal ablation therapies include:
- Irreversible Electroporation (IRE): Uses electrical pulses to create permanent pores in cancer cell membranes, destroying tumour cells and releasing tumour antigens while preserving surrounding structures.
- Electrochemotherapy (ECT): Combines electrical pulses with tumour-targeted chemotherapy to increase drug uptake, eliminating cancer cells while maintaining structural integrity.
- Photodynamic Therapy (PDT): Uses a light-activated reaction with documented immune-stimulating effects to destroy cancer cells while preserving antigen structure.
How This Improves Immunotherapy Response
While the immune system on its own can be effective in targeting cancer cells throughout the body, therapies that trigger an abscopal effect help initiate and enhance this response.
By preserving and releasing intact tumour antigens, non-thermal focal therapies increase tumour visibility to the immune system.
This creates a local immune response that immunotherapy can build on, rather than trying to initiate one from scratch. Once immune recognition is established, immunotherapy can amplify this response systemically, helping target cancer cells beyond the primary tumour.
This two-step approach supports stronger immune activation and helps improve the ability to target micrometastatic disease that cannot be detected on imaging.
Combining Focal Therapy With Immunotherapy
As discussed, immunotherapy is most effective when it builds on an existing immune response. In practice, this often involves combining systemic immunotherapy with non-thermal focal treatments that first improve tumour visibility.
One example of how this approach is applied involves a structured sequence of immune priming, tumour treatment, and post-treatment immune support:
- Immune priming: An initial treatment is administered prior to focal therapy to begin activating immune recognition.
- Systemic immune activation: A dose of immunotherapy is given before ablation to activate T-cell function throughout the body, preparing the immune system to respond.
- Focal ablation treatment: Non-thermal techniques such as IRE, ECT, or PDT are used to treat the primary tumour while releasing tumour antigens.
- Post-ablation immune support: Additional immunotherapy may be used after treatment to maintain immune activity as remaining cancer cells are identified and targeted.
The exact sequence and combination can vary depending on tumour characteristics and individual response, but the underlying principle remains the same: improve tumour visibility first, then amplify the response systemically.
Learn how Vitus applies immunotherapy with non-thermal focal treatments →
FAQs
Immunotherapy can be effective in prostate cancer, but results are often limited when used on its own. Prostate cancer is typically a “cold” tumour with low immune activity. Outcomes tend to improve when immunotherapy is combined with prostate cancer treatments that enhance immune recognition.
Prostate tumours often lack sufficient immune activity and T-cell presence. This means there is little existing immune response for immunotherapy to build on. Improving tumour visibility to the immune system is key to increasing effectiveness, particularly in advanced or metastatic disease.
Immunotherapy helps the body’s immune system identify and attack cancer cells. It works by enhancing T-cell activity and overcoming signals that suppress the immune response. It is most effective when used alongside treatments that improve immune recognition.
Immunotherapy alone is not typically considered a curative treatment for prostate cancer. Its role is to support the immune system in targeting prostate cancer cells throughout the body. When combined with other treatments, it helps contribute to longer-term disease control.
Immunotherapy is most effective when the tumour has been made more visible to the immune system. Treatments that expose tumour antigens can improve immune recognition. This allows immunotherapy to generate a stronger and more targeted response and help kill cancer cells more effectively.