Prostate cancer is a most common malignancy in men with little efficacy of standards of care once it reaches metastatic stage which underlines the importance of developing new treatment strategies such as immunotherapy. Human tumors recruit and expand populations of potently immunosuppressive myeloid-derived suppressor cells (MDSCs) which were associated with progression and poor patients’ survival. In the present study, the researchers have evaluated myeloid cell populations using flow cytometry on blood samples from patients followed by ex vivo functional assays. A population of granulocytic MDSCs that accumulate in patients’ circulation during prostate cancer progression was identified and shown to potently inhibit autologous T cells proliferation. The circulating MDSCs have high levels of activated STAT3, which is a central immune checkpoint regulator. Using RNA interference technology, the researchers were able to shut down the level of STAT3 and abrogate the immunosuppressive effects of patients-derived MDSCs on T cells. The study demonstrates the accumulation of granulocytic MDSCs with prostate cancer progression and the feasibility of using TLR9-targeted STAT3 siRNA delivery strategy to alleviate MDSC-mediated immunosuppression.
TLR9-targeted STAT3 silencing abrogates immunosuppressive activity of myeloid-derived suppressor cells from prostate cancer patients
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