Study Identifies a Potential Window for Immunotherapy During Androgen Deprivation Treatment

A new study published in the Journal for ImmunoTherapy of Cancer suggests that the timing of immunotherapy could be crucial in prostate cancer. Researchers found that androgen deprivation therapy (ADT) initially stimulates immune activity within prostate tumours, but this response gradually shifts towards immunosuppression as treatment continues.

The researchers examined prostatectomy specimens from 43 patients who had received neoadjuvant ADT, comparing them with matched untreated controls. Using RNA sequencing and multispectral immunofluorescence, they investigated how immune cell populations and their interactions with cancer cells changed according to treatment duration.

The strongest immune activation was observed after 3–5 months of ADT. During this period, tumours showed increased activity in pathways involved in antigen presentation and adaptive immunity, accompanied by substantial infiltration of CD8+ cytotoxic T cells and CD4+ helper T cells. Importantly, these immune cells were frequently located close to tumour cells, suggesting a more favourable environment for antitumour immune responses.

However, after six months or longer, the immune environment changed considerably. Cytotoxic T-cell infiltration decreased, while immunosuppressive M2-like macrophages and regulatory T cells became more prominent. These findings suggest that prolonged ADT may progressively favour mechanisms that limit immune activity.

The observations raise an intriguing possibility: administering immune checkpoint inhibitors during the initial immune activation period might improve their effectiveness in prostate cancer, a disease that has generally responded poorly to these treatments. Rather than introducing immunotherapy after hormonal resistance develops, earlier treatment could potentially exploit a temporary period of greater immune responsiveness.

However, this was an observational translational study, not a clinical trial testing immunotherapy. The relatively small sample consisted of patients treated before prostatectomy, and the findings cannot automatically be extended to metastatic disease or patients receiving long-term ADT.

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