RT Journal Article SR Electronic T1 Pancreatic cancer is marked by complement-high blood monocytes and tumor-associated macrophages JF Life Science Alliance JO Life Sci. Alliance FD Life Science Alliance LLC SP e202000935 DO 10.26508/lsa.202000935 VO 4 IS 6 A1 Kemp, Samantha B A1 Steele, Nina G A1 Carpenter, Eileen S A1 Donahue, Katelyn L A1 Bushnell, Grace G A1 Morris, Aaron H A1 The, Stephanie A1 Orbach, Sophia M A1 Sirihorachai, Veerin R A1 Nwosu, Zeribe C A1 Espinoza, Carlos A1 Lima, Fatima A1 Brown, Kristee A1 Girgis, Alexander A A1 Gunchick, Valerie A1 Zhang, Yaqing A1 Lyssiotis, Costas A A1 Frankel, Timothy L A1 Bednar, Filip A1 Rao, Arvind A1 Sahai, Vaibhav A1 Shea, Lonnie D A1 Crawford, Howard C A1 Pasca di Magliano, Marina YR 2021 UL https://www.life-science-alliance.org/content/4/6/e202000935.abstract AB Pancreatic ductal adenocarcinoma (PDA) is accompanied by reprogramming of the local microenvironment, but changes at distal sites are poorly understood. We implanted biomaterial scaffolds, which act as an artificial premetastatic niche, into immunocompetent tumor-bearing and control mice, and identified a unique tumor-specific gene expression signature that includes high expression of C1qa, C1qb, Trem2, and Chil3. Single-cell RNA sequencing mapped these genes to two distinct macrophage populations in the scaffolds, one marked by elevated C1qa, C1qb, and Trem2, the other with high Chil3, Ly6c2 and Plac8. In mice, expression of these genes in the corresponding populations was elevated in tumor-associated macrophages compared with macrophages in the normal pancreas. We then analyzed single-cell RNA sequencing from patient samples, and determined expression of C1QA, C1QB, and TREM2 is elevated in human macrophages in primary tumors and liver metastases. Single-cell sequencing analysis of patient blood revealed a substantial enrichment of the same gene signature in monocytes. Taken together, our study identifies two distinct tumor-associated macrophage and monocyte populations that reflects systemic immune changes in pancreatic ductal adenocarcinoma patients.