Roswell Park researchers identify timing window for immunotherapy in prostate cancer treatment

Researchers at Roswell Park Comprehensive Cancer Center, led by Dr. Kent Nastiuk, discovered that androgen deprivation therapy in prostate cancer temporarily boosts immune response before turning immunosuppressive after six months. Early in treatment, CD8+ and CD4+ T cells flood tumors, but tumor-associated macrophages later replace them. The findings, published in the Journal for ImmunoTherapy of Cancer, suggest a critical window to administer immune checkpoint inhibitors before resistance sets in.

Study analysis of immune dynamics

• ▪Research led by Dr. Kent Nastiuk analyzed prostatectomy specimens from treated patients to determine how neoadjuvant androgen deprivation therapy alters immune and inflammatory pathways in primary prostate tumors over time.
• ▪A Roswell Park Comprehensive Cancer Center study published in the Journal for ImmunoTherapy of Cancer found that neoadjuvant androgen deprivation therapy temporarily activates immune responses in prostate tumors before fading after six months.
• ▪The Roswell Park study in the Journal for ImmunoTherapy of Cancer reveals dynamic temporal immune changes that can guide the strategic timing of checkpoint pathway inhibitors in prostate cancer.

Immune changes during androgen deprivation

• ▪Roswell Park doctoral graduate Dr. Renyuan Zhang found that several months of neoadjuvant androgen deprivation therapy induced a robust influx of tumor-killing CD8⁺ and CD4⁺ T cells into prostate tumors.
• ▪According to Roswell Park researchers, prostate tumors develop resistance to immunotherapies after six months of androgen deprivation therapy due to an influx of inhibitory immune cells.
• ▪Prostate tumors exposed to six or more months of neoadjuvant androgen deprivation therapy exhibited increased tumor-associated macrophages and regulatory T cells that suppress cancer-killing T cells.

Proposed strategy for combining therapies

• ▪Study co-first author Dr. Anmbreen Jamroze stated that administering immune checkpoint inhibitors during the early temporal window of androgen deprivation therapy provides a rationale to maximize therapeutic benefit.
• ▪Roswell Park researchers proposed sequencing prostate cancer treatments by applying immune checkpoint inhibitors shortly after initiating androgen deprivation therapy, before immunosuppressive resistance develops.
• ▪Roswell Park assistant professor Dr. Kent Nastiuk suggested combining anti-androgen therapy with rapid follow-up immunotherapy for aggressive prostate tumors rather than waiting for disease progression.

Challenges in existing prostate cancer treatments

• ▪Patients with advanced and recurrent prostate cancer are treated with androgen deprivation therapy, but how immune-tumor interactions evolve during treatment has remained unclear.
• ▪Immune checkpoint inhibitors have historically failed in human prostate cancers partly because prior studies relied on preclinical models or static single time-point clinical data.