Inflammatory networks and T cell immunosurveillance in pancreatic cancer

TL;DRAbstract

Cancer-associated inflammation plays a decisive role in restraining anti-tumor immunity, particularly in pancreatic ductal adenocarcinoma (PDA) for which a massive infiltration of immunosuppressive leukocytes into tumor stroma accompanies cancer growth. Gr-1+ CD11b+ cells, often called myeloid-derived suppressor cells (MDSCs), are a key feature of cancer-related inflammation in this disease, but the crosstalk between Gr-1+ CD11b+ cells and PDA tumor cells remains incompletely understood. Here, using a genetically engineered mouse model of invasive PDA, we show that Gr-1+ CD11b+ myeloid cells accumulate in primary and metastatic lesions, exhibit high levels of arginase and iNOS activity, and potently inhibit proliferation of antigen-specific T cells. Among the many cytokines and chemokines produced by PDA tumors, GM-CSF was both necessary and sufficient to drive proliferation and differentiation of c-kit + Gr-1neg CD11bneg splenocytes from tumor-bearing mice into functional MDSCs. in vi

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