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

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.

Effects of particulate matter exposure on the expression of the SARS-CoV-2 ACE2 receptor in ocular surface tissues and cells.

Particulate matter (PM) has been reported to be one of the risk factor for COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, although the ocular surface is deeply affected by both PM exposure and SARS-COV-2 infection, no studies have investigated the effects of PM exposure on the ocular route of SARS-COV-2 infection. To this end, we explored the effects of PM on the expression of SARS-COV-2-associated receptors and proteins in ocular surface. Herein, short- and long-term PM-exposed rat models were established by topically administering PM for 3 and 10 days, respectively. Immortalized human corneal epithelial cells (HCECs) and human conjunctival epithelial cells (HCjECs) were exposed to PM. ACE2, TMPRSS2, CD147, and ADAM17 expression levels were measured by western blot analysis. Our results show that short-term PM exposure had little effect on the expressions of ACE2, TMPRSS2, and CD147 in ocular surface tissues. However, long-term PM exposure decreased the ACE2 expression in conjunctival tissues and increased the CD147 expression in corneal or conjunctival tissues. PM exposure reduced the ACE2 expression by increasing the ADAM17 expression and ACE2 shedding level in HCECs and HCjECs. Our findings suggest that long-term PM exposure down-regulate the expression of the SARS-CoV-2 receptor ACE2 in conjunctival tissues through ADAM17-dependent ACE2 shedding. However, long-term PM exposure up-regulates the expression of another SARS-CoV-2 receptor CD147 in ocular surface tissues, accompanied by ocular surface damage and cytotoxicity. This study provides a new insight into uncovering potential risk factors for infection with SARS-CoV-2 via the ocular route.