Combined chemotherapy and immunotherapy shows promise for advanced prostate cancers. Immune cell manipulation plus chemotherapy achieves prostate cancer remission in mouse models where chemotherapy alone fails, which was reported on April 29 in the presitgious journal Nature.
Advanced or metastatic prostate cancer does not typically respond to chemotherapy. Prostate cancers also fail to respond to a promising new type of immunotherapy drugs called checkpoint inhibitors, which disable cancer cells’ cloaking mechanism so that a person’s own immune system can better fight the tumor. This specific resistance is likely due in part to immunosuppressive B cells, which are more common in larger prostate tumors in mice, as well as in advanced and metastatic prostate cancer in humans. As the name suggests, these cells keep the immune system at bay, rendering most therapies ineffective and allowing malignant tumors to grow unchecked.
In this study, researchers worked with three different mouse models of advanced prostate cancer. All three models were resistant to low doses of the chemotherapy drug oxaliplatin, which has the unique ability to activate cancer-killing immune cells. But when the researchers blocked the development or function of immunosuppressive B cells or removed them entirely before treating the mice with low-dose oxaliplatin, the prostate tumors were almost completely destroyed by the mice’s own immune cells. The team got similar results when low-dose oxaliplatin was combined with a checkpoint inhibitor.
“The presence of such B cells in human prostate cancer calls for immediate clinical testing of this novel therapeutic approach,” said Shabnam Shalapour, PhD, postdoctoral researcher and first author of the study.
Prostate cancer is the second leading cause of cancer-related death in American men. About one in seven men will be diagnosed with prostate cancer during their lifetimes.
“In addition to prostate cancer, similar immunosuppressive B cells can be detected in other human cancers,” said Prof. Lukas Kener of the Ludwig Boltzmann Institute for Cancer Research. “This indicates that B cell-mediated immunosuppression might be the reason several other cancers are also unresponsive to checkpoint inhibitors, raising the hope that chemoimmunotherapy will have broader applications for many cancer types.”
Study co-authors include Michael Karin, Joan Font-Burgada, Giuseppe Di Caro, Zhenyu Zhong, Elsa Sanchez-Lopez, Debanjan Dhar, Massimo Ammirante, Amy Strasner, Donna E. Hansel, Christina Jamieson, Christopher J. Kane, UC San Diego; Gerald Willimsky, Charite-Medical University of Berlin; Tobias Klatte, Peter Birner, Medical University Vienna; Lukas Kenner, Ludwig Boltzmann Institute for Cancer Research.
The original publication in Nature you can find here, which was commented on by Zitvogel and Kroemer and an editorial is available here