PT  - JOURNAL ARTICLE
AU  - Samantha B Kemp
AU  - Nina G Steele
AU  - Eileen S Carpenter
AU  - Katelyn L Donahue
AU  - Grace G Bushnell
AU  - Aaron H Morris
AU  - Stephanie The
AU  - Sophia M Orbach
AU  - Veerin R Sirihorachai
AU  - Zeribe C Nwosu
AU  - Carlos Espinoza
AU  - Fatima Lima
AU  - Kristee Brown
AU  - Alexander A Girgis
AU  - Valerie Gunchick
AU  - Yaqing Zhang
AU  - Costas A Lyssiotis
AU  - Timothy L Frankel
AU  - Filip Bednar
AU  - Arvind Rao
AU  - Vaibhav Sahai
AU  - Lonnie D Shea
AU  - Howard C Crawford
AU  - Marina Pasca di Magliano
TI  - Pancreatic cancer is marked by complement-high blood monocytes and tumor-associated macrophages
AID  - 10.26508/lsa.202000935
DP  - 2021 Jun 01
TA  - Life Science Alliance
PG  - e202000935
VI  - 4
IP  - 6
4099  - https://www.life-science-alliance.org/content/4/6/e202000935.short
4100  - https://www.life-science-alliance.org/content/4/6/e202000935.full
SO  - Life Sci. Alliance2021 Jun 01; 4
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.