Immunosuppressive roles of IL-22 receptor-expressing myeloid cells in the progression of pancreatic ductal adenocarcinoma

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and fatal tumors worldwide. However, current biomarkers of PDAC remain inaccurate and imprecise for diagnosis. Here, we found that IL-10R2+/IL-22R1+ myeloid cells were increased in the blood and PDAC tissues of xenograft/orthotopic murine PDAC models. The increase in the population of IL-10R2+/IL-22R1+ myeloid cells in the blood of the xenograft murine model was dependent on the tumor size, which suggests that IL-10R2+/IL-22R1+ myeloid cells could be a liquid biopsy marker. In the orthotopic model, the population of IL-10R2+/IL-22R1+ myeloid cells increased in PDAC cell line injected group. Moreover, the population of IL-10R2+/IL-22R1+ myeloid cells also increased on day 7 after the injection, which is considered the early stage in the model. These results indicate that IL-10R2+/IL-22R1+ myeloid cells could be a biomarker of early PDAC. Furthermore, IL-10R2+/IL-22R1+ myeloid cells showed immunosuppressive effects. Notably, T cells co-cultured with IL-10R2+/IL-22R1+ myeloid cells showed decreased proliferation rate and cytotoxicity. Induction of differentiation into myeloid-derived suppressor cells increased the expression of IL-10R2 and IL-22R1 in human blood. Additionally, T cells cocultured with IL-10R2+/IL-22R1+ myeloid cells exhibited diminished proliferation. Therefore, IL-10R2+/IL-22R1+ myeloid cells could be a liquid biopsy marker or early-stage biomarker of PDAC and could possess immunosuppressive features.