Turning a Cold Tumor Hot: New Advances in Immunotherapy for Prostate Cancer

Researchers are making strides in enhancing the effectiveness of immunotherapy for prostate cancer, a disease that has historically been less responsive to this type of treatment compared to cancers like melanoma and lung cancer. A recent clinical trial suggests that combining a new generation immunotherapy drug with standard hormone therapy, administered before surgery, could significantly improve the immune system’s ability to fight the disease.

The Challenge of “Cold” Tumors

Prostate cancers are often described as “immune-cold” tumors, meaning they don’t naturally attract a sufficient number of immune cells to mount a robust attack against the cancer. This lack of immune activity has been a major hurdle in applying immunotherapy successfully. While androgen deprivation therapy (ADT), a cornerstone of prostate cancer treatment, can temporarily increase immune cell presence within the tumor, this effect is fleeting.

How ADT Impacts the Immune Response

ADT works by attracting immune cells, particularly CD8+ T cells (which can kill cancer cells), to the tumor site. However, ADT similarly triggers an increase in regulatory T lymphocytes (Tregs). Tregs act as suppressors of the immune system, effectively counteracting the anti-tumor effects of the initial immune cell influx. This creates a complex immunological environment that limits the potential of immunotherapy.

A Novel Approach: Targeting Tregs

A recent multicenter study, coordinated by Mayo Clinic and published in Cell Reports Medicine, investigated whether adding a new immunotherapy to hormone therapy before surgery could overcome this Treg-mediated immune suppression. The trial involved 24 men with high-risk, localized prostate cancer – meaning they didn’t have metastatic cancer but were at a high risk of the cancer spreading.

The Trial: Combining ADT with BMS-986218

The study evaluated the combination of ADT with an experimental anti-CTLA-4 antibody called BMS-986218, which is currently under clinical investigation and not yet approved for general use. CTLA-4 is a molecule highly expressed on Tregs, particularly within tumors. BMS-986218 was specifically designed to more effectively reduce the number of these immunosuppressive cells compared to earlier therapies in the same class.

Key Findings: Reduced Tregs and Improved Outcomes

The results demonstrated that combining hormone therapy with the experimental antibody significantly reduced the levels of Tregs within the tumors compared to hormone therapy alone. Importantly, patients who experienced the greatest reduction in Tregs were more likely to remain cancer-free during the follow-up period. This suggests a direct link between Treg reduction and improved clinical outcomes.

Analyzing Tumor Changes Before Surgery

Administering the treatment regimen before surgery allowed researchers to analyze extensive tissue samples from the removed tumors, providing a detailed look at the changes occurring within the immune cell populations. This enabled the use of advanced technologies to evaluate the impact of the treatment on different types of immune cells within the prostate tumor.

Future Directions and Biomarker Identification

According to the study authors, this research provides the first clinical evidence that a modified anti-CTLA-4 therapy can selectively reduce Tregs in prostate tumors. The data also offer valuable insights for identifying patients who are most likely to benefit from this approach and for establishing potential biomarkers to guide future studies. Columbia University researchers are also actively investigating similar strategies to “heat up” cold tumors.

Expanding Immunotherapy Options for Prostate Cancer

Beyond targeting Tregs, ongoing clinical trials are exploring a range of immunotherapy approaches for prostate cancer, including CAR-T cell therapy, vaccines, and IL-15 agonists. OncoDaily reports that these trials are expanding immunotherapy’s reach into earlier stages of the disease, aiming for deeper remissions and potential cures. MD Anderson Cancer Center is also investigating T cell bi-specifics, which redirect T cells to attack tumor cells, even in tumors with low T cell counts.

The National Cancer Institute (NCI) supports numerous clinical trials focused on improving prostate cancer treatment, offering patients opportunities to participate in cutting-edge research.