A new study published in the journal Nature revealed a promising new combination therapy for advanced prostate cancers that are typically non-responsive to chemotherapy. The study is entitled “Immunosuppressive plasma cells impede T-cell-dependent immunogenic chemotherapy” and was conducted by a team led by researchers at the University of California, San Diego.
Prostate cancer is the second most common cancer in men, with almost one million new cases diagnosed every year worldwide. It is estimated that one in every seven men will be diagnosed with this cancer during their lifetimes. It is a curable cancer that can range from slow-growing tumors (more common) to rapidly progressing aggressive tumors. Advanced or metastatic prostate cancers usually are non-responsive to chemotherapy.
Prostate cancers are also non-responsive to an encouraging new type of drugs based on immunotherapy called checkpoint inhibitors, which are drugs able to trigger a stronger immune response to better fight cancer. It has been suggested that this resistance to treatment is in part due to the accumulation of cells that suppress the body’s immune response, namely immunosuppressive immune B cells. These cells can control the immune system, negatively interfering with cancer therapies and allowing the growth of malignant tumors despite treatment. Immunosuppressive B cells are often found in larger prostate cancers in mice and in advanced and metastatic prostate cancers in humans.
In the study, researchers used three distinct rodent models of advanced prostate cancer, all resistant to low doses of oxaliplatin, a chemotherapy drug able to activate cancer-killing immune cells and an effective agent in aggressive prostate cancers. Researchers found that when immunosuppressive B cells were blocked or entirely removed prior to low-dose oxaliplatin treatment in mice, prostate cancers were nearly completely eliminated by the immune system. Similar results were obtained when low-dose oxaliplatin was tested together with a checkpoint inhibitor.
“The presence of such B cells in human prostate cancer calls for clinical testing of this novel therapeutic approach,” said the study’s lead author Dr. Shabnam Shalapour in a news release.
The research team concluded that blocking or removing these immunosuppressive B cells together with chemotherapy enables the elimination of prostate tumors. This novel combination therapy based on immune cell manipulation and chemotherapy, named chemoimmunotherapy, allowed an almost complete remission of advanced prostate cancer in mouse models.
“In addition to prostate cancer, similar immunosuppressive B cells can be detected in other human cancers,” noted the study’s senior author Dr. Michael Karin. “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.”
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