Tumour-associated myeloid cells expressing IL-10R2/IL-22R1 as a potential biomarker for diagnosis and recurrence of pancreatic ductal adenocarcinoma

Abstract

Background: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with a poor survival rate, largely due to the lack of early diagnosis. Although myeloid cells are crucial in the tumour microenvironment, whether their specific subset can be a biomarker of PDAC progression is unclear.

Methods: We analysed IL-22 receptor expression in PDAC and peripheral blood. Additionally, we analysed gene expression profiles of IL-10R2⁺/IL-22R1⁺ myeloid cells and the presence of these cells using single-cell RNA sequencing and murine orthotropic PDAC models, respectively, followed by examining the immunosuppressive function of IL-10R2⁺/IL-22R1⁺ myeloid cells. Finally, the correlation between IL-10R2 expression and PDAC progression was evaluated.

Results: IL-10R2⁺/IL-22R1⁺ myeloid cells were present in PDAC and peripheral blood. Blood IL-10R2⁺ myeloid cells displayed a gene expression signature associated with tumour-educated circulating monocytes. IL-10R2⁺/IL-22R1⁺ myeloid cells from human myeloid cell culture inhibited T cell proliferation. By mouse models for PDAC, we found a positive correlation between pancreatic tumour growth and increased blood IL-10R2⁺/IL-22R1⁺ myeloid cells. IL-10R2⁺/IL-22R1⁺ myeloid cells from an early phase of the PDAC model suppressed T cell proliferation and cytotoxicity. IL-10R2⁺ myeloid cells indicated tumour recurrence 130 days sooner than CA19-9 in post-pancreatectomy patients.

Conclusions: IL-10R2⁺/IL-22R1⁺ myeloid cells in the peripheral blood might be an early marker of PDAC prognosis.