Preclinical Studies Show Many Androgen-Deprivation Therapies May Suppress Adaptive Immune Responses
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 led by UT Southwestern Medical Center investigators. Researchers using mouse models found that many medical androgen-deprivation therapies—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.
Their findings were published by Pu et al in Science Translational Medicine.
“Medical androgen-deprivation therapies 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, MD, PhD, Professor of Pathology and Immunology at UT Southwestern.
Link to Relapse
Relapse of prostate tumors, however, has been a major problem.
“While surgical androgen-deprivation therapy—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 Dr. 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.
“Our study shows that in some patients, this poor response could also be due to the radiation or chemotherapy itself suppressing the immune response,” Dr. 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 is key to maximizing the antitumor effects of combination therapy, the study indicates.
“The findings also highlight an underappreciated mechanism of androgen receptor 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,” Dr. Fu said.
“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.”
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
