Malignant Ascites Harbors Immune Niche with IL-10 Enriched Effector Dysfunction and Persistent Cancer-Binding IgG
Elana R. Shaw, Alexei G. Hernandez, Linda Huang, Bryan C. Szeglin, Yuqian Wang, Carolyn M. Merwanji, Rosela Golloshi, Matthew Dunworth, Shannon N. Radomski, Charles Lim, David Lichtman, Patrick Balao, John Texter, John Woller, Christopher J. VandenBussche, Patrizio Caturegli, LuAnn Rezavi, Conlan Tran, Christopher J. Thoburn, Joel S. Bader, Felipe Andrade, Maximilian F. Konig, Won Jin Ho, Andrew J. EwaldAbstract
Malignant ascites provides a window into cancer-immune interactions in the peritoneal cavity. Using Cytometry by Time of Flight (CyTOF), we analyzed ascitic immune cells collected from patients with advanced gastrointestinal cancers, nonmalignant forms of hepatitis (NMH), and healthy control peripheral blood mononuclear cells (HC PBMCs). Compositionally, ascitic immune cells shared a myeloid-rich, B and naïve T cell-low signature relative to HC PBMCs. Underneath the shared ascitic compositional signature, three major functional immunophenotypes emerged in response to exogenous stimulation along a suppressive to cytotoxic axis, aligning with Luminex measurements of ascitic cytokine levels: IL-10 enriched, Nonpolarized, and Granzyme B (GZMB) enriched. In our cohort, the IL-10 enriched functional immunophenotype was exclusive to samples from patients with cancer while the GZMB enriched response was dominated by NMH samples. Ascites from patients with pancreatic ductal adenocarcinoma (PDAC) contained a persistent anti-cancer humoral response characterized by IgG that bound to autologous ascitic PDAC cells and multiple allogeneic PDAC cell lines.