Genetic ‘Immune Landscape’ Determines Progression of Prostate Cancer, Mice Study Suggests

Genetic ‘Immune Landscape’ Determines Progression of Prostate Cancer, Mice Study Suggests
Genetic variations that drive prostate cancer dictate the composition of immune cells within tumors and response to treatment, a new study shows. Researchers at the Beth Israel Deaconess Medical Center (BIDMC) suggest that profiling a patient's tumor could help tailoring immunotherapies and identify patients who are most responsive to certain treatments. The research, “Diverse genetic-driven immune landscapes dictate tumor progression through distinct mechanisms,” was published in the journal Nature Medicine. Diverse genetic mutations can cause prostate cancer, the most common cancer in American men other than skin cancer. One example is the tumor suppressor gene Pten, whose complete loss is linked to metastasis and disease progression in prostate cancer. In addition to gene mutations, the tumor microenvironment (the non-cancerous cells present in the tumor, including immune cells and cells comprising blood vessels), is also an important factor in disease progression and response to treatment. The investigators created mouse models of four known genetic alterations of human prostate cancer, including deletion of Pten alone, or in combination with tumor suppressor genes Trp53, Zbtb7a, or Pml. Results showed striking differences in the types and numbers of immune cells present in the tumor’s microenvironment, also called the tumor's "immune landscape". These differences increased over time. "We observed that specific genetic events resulted in striking differences in the composition of immune cells present in and around the tumor - results with important therapeutic implications," Pier Paolo Pandolfi, MD, PhD, the study’s senior author, said in a press release. Pandolfi also is director of the Cancer Center and Cancer Research Institute
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