Myeloid-derived suppressor cells (MDSCs) are immune cells that "expand" when faced with cancer, inflammation or infections. MDSCs have the unique ability to suppress the body's T-cell response to disease.
Now, a new study shows that MDSCs may be important in developing treatments for advanced prostate tumor.
The tumor microenvironment is made up of a mixture of fibroblasts, infiltrating immune cells and other cells, proteins and signaling molecules. MDSCs are infiltrating immune cells that promote tumors through their striking lack of immunological response.
Prior studies have identified a direct tie between MDSC and tumors. However, the role of MDSC in cancer progress, particularly in prostate cancer, has been not very clear.
The researchers used a new prostate cancer mouse model and patient cancer samples to demonstrate that depletion of MDSCs suppresses tumor progression. Additionally, they also showed that a cell signaling pathway called Hippo-Yap1 regulated the protein Cxcl5, which was identified as a cancer-secreted chemokine that attracted or recruited MDSCs which expressed another protein, Cxcr2. By blocking the Cxcr2 proteins with small molecule inhibitors, tumor progress was impeded. They also revealed that silencing of Yap1 expression in established tumors led to a reduction in MDSC infiltration and inhibition of tumor growth.
Pharmacologic elimination of MDSCs or blockage of the Cxcl5-Cxcr2 signaling pathway resulted in robust anti-tumor response in vivo and prolonged survival. The targeting of either MDSC recruitment or infiltrated MDSCs may represent a valid therapeutic opportunity in treating advanced prostate cancer.
Further studies may be focusing on combining MDSC inactivation with immunotherapy, including immune checkpoint inhibitors such as anti-CTLA4, anti PD1 and anti-PD-L1 antibodies.
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