Combination Immunotherapy Reduces Immune-Suppressing Cells in High-Risk Prostate Cancer, Improving Patient Outcomes
A multi-institutional study, led by Mayo Clinic and published in Cell Reports Medicine, investigated the effects of combining a next-generation immunotherapy with standard hormone therapy (androgen deprivation therapy or ADT) in patients with high-risk, localized early-stage prostate cancer prior to surgery. The research indicated that this combination therapy led to a reduction in regulatory T cells (Tregs) within prostate tumors. Patients whose tumors showed the most significant Treg reductions demonstrated a higher likelihood of remaining cancer-free during follow-up.
Study Background
Prostate cancer tumors are often characterized as "immunologically cold," meaning they do not effectively attract immune cells to mount an anti-cancer response. Standard hormone therapy, ADT, is a common treatment. While ADT can temporarily increase the presence of immune cells in tumors, it also elevates regulatory T cells (Tregs), which can suppress the immune system's anti-cancer activity. Selective depletion of Tregs in tumors has been a long-standing objective in oncology.
Research Design and Intervention
The study, a first-in-human, early-phase randomized trial, involved 24 men diagnosed with high-risk, localized prostate cancer. Researchers aimed to determine if adding an investigational Fc-enhanced anti-CTLA-4 antibody, identified as BMS-986218, to hormone therapy could counteract the immune suppression caused by elevated Tregs. This engineered anti-CTLA-4 drug specifically targets CTLA-4, a protein highly expressed on Tregs, particularly within tumors.
Key Findings
The combination therapy, which included BMS-986218, significantly decreased intratumoral Tregs compared to hormone therapy administered alone.
Patients who experienced the largest reductions in Tregs within their tumors also exhibited a greater likelihood of remaining cancer-free during the follow-up period.
Dr. Casey Ager, a cancer immunology researcher at Mayo Clinic and the study's first author, noted that the trial provided an opportunity to evaluate a new immunotherapy in localized prostate cancer patients at high risk of progression. The research also represents the first clinical evidence that an engineered anti-CTLA-4 therapy can reduce regulatory T cells within prostate tumors.
The pre-surgical administration of the treatment allowed for a detailed analysis of surgically removed prostate tumors. This provided insights into how the immunotherapy impacted the complex immune environment of prostate cancer at an individual immune cell level, potentially identifying patient beneficiaries and suggesting biomarkers for future trials.
Implications
These findings provide data that supports the development of evidence-based immunotherapy approaches for early-stage prostate cancer patients. The research aims to contribute to the understanding of immunotherapy's clinical viability in early-stage prostate cancer, potentially supporting efforts to prevent the progression of the disease.