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

• Published in: British journal of cancer 2024-06, Vol.130 (12), p.1979-1989
• Main Authors: Lee, Hyung Keun, Kim, So Young, Chung, Soo-Hyun, Choi, Bongkun, Kim, Ji-Eun, Yoon, Dohee, Jang, Sung Ill, Yeo, Areum, Kang, Hyun Goo, Lee, Jusung, Choi, Yoon Ha, Park, Joon Seong, Sung, Yoolim, Kim, Jong Kyoung, Chang, Eun-Ju, Lee, Dong Ki
• Format: Article
• Language: English
• Subjects: 631/250/580/1884; 692/53/2421; Adenocarcinoma; Animal models; Animals; Biomarkers; Biomarkers, Tumor - blood; Biomarkers, Tumor - genetics; Biomedical and Life Sciences; Biomedicine; Cancer Research; Carcinoma, Pancreatic Ductal - blood; Carcinoma, Pancreatic Ductal - diagnosis; Carcinoma, Pancreatic Ductal - genetics; Carcinoma, Pancreatic Ductal - pathology; Cell culture; Cell growth; Cell Line, Tumor; Cell proliferation; Cytotoxicity; Diagnosis; Drug Resistance; Epidemiology; Female; Gene expression; Humans; Interleukin-10 Receptor beta Subunit - genetics; Lymphocytes T; Male; Malignancy; Medical diagnosis; Medical prognosis; Mice; Molecular Medicine; Monocytes; Myeloid cells; Myeloid Cells - metabolism; Myeloid Cells - pathology; Neoplasm Recurrence, Local - genetics; Neoplasm Recurrence, Local - pathology; Oncology; Pancreas; Pancreatic cancer; Pancreatic Neoplasms - blood; Pancreatic Neoplasms - diagnosis; Pancreatic Neoplasms - genetics; Pancreatic Neoplasms - pathology; Peripheral blood; Receptors, Interleukin - genetics; Tumor microenvironment; Tumor Microenvironment - genetics; Tumors
• ISSN: 0007-0920; 1532-1827; 1532-1827
• DOI: 10.1038/s41416-024-02676-w

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.