A new form of immunotherapy reactivates the response to hormone treatment in advanced prostate cancer, a study in mice and human prostate cancer cells has found.

Hormone therapy is a mainstay of prostate cancer treatment—but tumor cells can grow resistant, leading to a hard-to-treat, advanced form of the disease.

The new study found that blocking a protein produced by a type of immune cell—known as granulocytic myeloid-derived suppressor cells—restored sensitivity to hormone therapy.

Drugs that block this protein, called IL-23, already exist and are used for autoimmune diseases, such as the skin condition psoriasis.

Clinical trials are now planned to assess the possible benefit of this new form of immunotherapy alongside the next-generation hormone therapy enzalutamide, in men with advanced prostate cancer.

Unpicking the role of myeloid-derived suppressor cells

Scientists at The Institute of Cancer Research, London, worked with colleagues at the Institute of Oncology Research in Switzerland on the study, which was published in the prestigious journal Nature today.

The research was supported by funders including the Prostate Cancer Foundation in the US, Prostate Cancer UK, the Movember Foundation, and Cancer Research UK.

The researchers studied mice, along with tumor and blood samples from prostate cancer patients treated at The Royal Marsden NHS Foundation Trust, to unpick the role of myeloid-derived suppressor cells in prostate cancer.

They found that blood and tumor samples from men with resistant prostate cancer contained higher levels of these suppressor immune cells and IL-23 than those from men whose cancer still responded to hormone therapy.

When they studied mice with prostate cancer that no longer produced IL-23, they found their tumors shrank considerably, and cancer cells grew more slowly.

It also took longer for the prostate tumors to become resistant to hormone therapy, and the mice survived for a longer period of time.

Both blocking IL-23 and stopping suppressor cells from moving into the tumor led to an improved response to hormone therapy, giving the researchers confidence that they identified a key mechanism that drives hormone therapy resistance in prostate cancer.

The researchers believe that IL-23 allows prostate cancer cells to sidestep the need for androgen hormones to fuel their growth.

Other immunotherapies, which work by reactivating the immune system’s ability to recognize and kill cancer cells, have shown some promise in prostate cancer, but only a subset of men respond well.

As myeloid-derived suppressor cells are present in many prostate tumors, the researchers believe that this immunotherapy approach could work in a large proportion of men with the disease.

Keen to start clinical trials

Professor Johann de Bono, Regius Professor of Cancer Research at The Institute of Cancer Research, London, and Consultant Medical Oncologist at The Royal Marsden NHS Foundation Trust, said:

“Hormone therapy works well in men with prostate cancer, but when cancer evolves to become resistant to treatment, other options are greatly reduced.”

“Our study found an important interaction between hormone signaling and the immune system. We believe we could exploit this to reverse hormone resistance in prostate cancer, and boost the effect of widely used prostate cancer drugs such as enzalutamide.”

“We are keen to start clinical trials to investigate how we can combine this new form of immunotherapy with existing hormone therapies, to improve treatment for men with advanced prostate cancer.”