News | Prostate Cancer | April 08, 2016

Common Prostate Cancer Treatments Suppress Immune Response, May Promote Relapse

Researchers suggest careful consideration of timing, combination of chemo- and radiation therapies

April 8, 2016 — Prostate cancer patients and their doctors may want to think twice about the best timing for chemotherapy or radiation therapy in conjunction with a common nonsurgical treatment, based on international research findings. The study was led by UT Southwestern Medical Center investigators.

Researchers using mouse models found that many medical androgen deprivation therapies (ADTs) — the most commonly used nonsurgical treatments for prostate cancer — may suppress patients’ adaptive immune responses, preventing immunotherapies from working if both treatments are used but not sequenced properly. ADTs are anti-hormone therapies that decrease the body’s levels of androgens, the type of hormone that is required for prostate cancer to survive and grow.

The study findings were published this week in Science Translational Medicine.

“Medical ADTs have been used for a half-century to treat prostate cancer, and promising clinical results for cancer immunotherapy have led to attempts to combine it and other standard-of-care therapies with immunotherapy to treat the disease,” said senior author and principal investigator Yang-Xin Fu, M.D., Ph.D., professor of pathology and immunology.

Relapse of prostate tumors, however, has been a major problem.

“While surgical ADT — castration — works well with immunotherapy, we determined that some androgen receptor antagonists could reduce the T-cell response against prostate cancer, leading to early tumor relapse,” said Fu, who holds the Mary Nell and Ralph B. Rogers Professorship in Immunology and also is a member of the Harold C. Simmons Comprehensive Cancer Center at UT Southwestern.

In other words, the suppressed immune response caused by medical ADTs blocks the efficacy of immunotherapy and leads to the relapses in cancer commonly seen in clinical trials.

“Our study shows that in some patients, this poor response could also be due to the radiation or chemotherapy itself suppressing the immune response,” Fu explained. “These treatments may reduce the tumor burden in the short term, but at the same time, they can suppress the immune response — and because they don’t kill every cancer cell, resistant clones will be selected, especially when the body’s immune response is not mobilized, and the tumor will relapse much more aggressively.

Careful regulation of the timing, types and dosage of antiandrogens used with immunotherapy are key to maximizing the anti-tumor effects of combination therapy, the study indicates.

“The findings also highlight an underappreciated mechanism of androgen receptor (AR) antagonist-mediated immune suppression and provide a new strategy to enhance the immune response and perhaps prevent or delay the relapse of advanced prostate cancer,” Fu said.

More studies are needed, Fu said, but the upshot is that some chemotherapies and radiation therapies should not be used concurrently with immunotherapies.

“We hope that our findings will cause physicians to think twice before starting chemotherapy or radiation on their cancer patients, to consider the best way to combine them with immunotherapies,” he said. “The idea is to kill the tumor cells while also considering whether these therapies are suppressing or activating the immune system.”

Lead author of the study was Yang Pu, a visiting junior researcher in pathology. Researchers from the University of Chicago, South China University of Technology, Chinese Academy of Sciences and Shanghai Jiao Tong University in China also contributed. The study was supported by grants from the National Institutes of Health and China’s Ministry of Science and Technology.

For more information: www.stm.sciencemag.org

Related Content

The FLASH Effect significantly improves the therapeutic ratio for curing cancer

The FLASH Effect significantly improves the therapeutic ratio for curing cancer

News | Radiation Oncology | July 28, 2021
July 28, 2021 — IntraOp Medical Corporation announced that ...
Recommendations address when and how radiation therapy should be used and outline best practices for patient-centered care

Figure 1. The guideline also includes treatment algorithms for initial local management (Figure 1) and local management following an unplanned excision (Figure 2).

News | Radiation Therapy | July 27, 2021
July 27, 2021 — A ...
64-Year-Old Man With Clear Cell Likelihood Score (ccLS) 5 Renal Masses

64-Year-Old Man With Clear Cell Likelihood Score (ccLS) 5 Renal Masses. Coronal T2-weighted single shot fast spin echo and coronal T1-weighted fat-saturated spoiled gradient echo acquired during corticomedullary phase—ccLS5 lesion outlined red for clarity.

News | Magnetic Resonance Imaging (MRI) | July 22, 2021
The 15-ton compact accelerator is lifted into the David C. Pratt Cancer Center at Mercy St. Louis. (Photo: Business Wire)

The 15-ton compact accelerator is lifted into the David C. Pratt Cancer Center at Mercy St. Louis. (Photo: Business Wire)

News | Radiation Oncology | July 21, 2021
July 23, 2021 — Mevion Medical Systems announced that it has delivered the 15-ton compact accelerator to...
Registration is now open for the Radiological Society of North America (RSNA) 107th Scientific Assembly and Annual Meeting, the world’s largest annual radiology forum, to be held at McCormick Place Chicago, Nov. 28 – Dec. 2, 2021

Getty Images

News | RSNA | July 21, 2021
July 21, 2021 — Registration is now open for the Radiological Society of North America (...
ASTRO just issued the following statement in response to the Radiation Oncology Model update in yesterday's HOPPS proposed rule, which compounds significant and detrimental cuts to the cancer care specialty in the proposed 2022 MPFS

Getty Images

News | Radiation Therapy | July 20, 2021
July 20, 2021 — In response to consecutive weeks of proposed...
Artificial intelligence-powered diagnostic tool spots asymptomatic prostate cancer in seconds

(L-R) Associate Professor Peter Brotchie (St Vincent's), Dr Ruwan Tennakoon (RMIT), Professor John Thangarajah (RMIT), Dr Mark Page (St Vincent's). Image courtesy of St Vincent's Hospital Melbourne

News | Prostate Cancer | July 19, 2021
July 19, 2021 — Prostate cancer is the most diagnosed