The Neonatal Fc Receptor Is Elevated in Monocyte-Derived Immune Cells in Pancreatic Cancer

Abstract

The neonatal Fc receptor (FcRn) is responsible for recycling of IgG antibodies and albumin throughout the body. This mechanism has been exploited for pharmaceutic delivery across an array of diseases to either enhance or diminish this function. Monoclonal antibodies and albumin-bound nanoparticles are examples of FcRn-dependent anti-cancer therapeutics. Despite its importance in drug delivery, little is known about FcRn expression in circulating immune cells. Through time-of-flight mass cytometry (CyTOF) we were able to characterize FcRn expression in peripheral blood mononuclear cell (PBMC) populations of pancreatic ductal adenocarcinoma (PDAC) patients and non-cancer donors. Furthermore, we were able to replicate these findings in an orthotopic murine model of PDAC. Altogether, we found that in both patients and mice with PDAC, FcRn was elevated in migratory and resident classical dendritic cell type 2 (cDC2) as well as monocytic and granulocytic myeloid-derived suppressor cell (MDSC) populations compared to tumor-free controls. Furthermore, PBMCs from PDAC patients had elevated monocyte, dendritic cells and MDSCs relative to non-cancer donor PBMCs. Future investigations into FcRn activity may further elucidate possible mechanisms of poor efficacy of antibody immunotherapies in patients with PDAC.

Systemic Neutrophil Gelatinase-Associated Lipocalin Alterations in Chronic Pancreatitis: A Multicenter, Cross-Sectional Study

“…PBMCs were thawed and processed as previously described ( 21 ). PBMCs were stained using the Maxpar Direct Immune Profiling Assay kit (PN 400286 B1; Standard BioTools, San Francisco, CA) with the addition of CD11b (Standard BioTools) and CD33 (BioLegend, San Diego, CA) antibodies (see Supplementary Table 2, Supplementary Digital Content 1, http://links.lww.com/CTG/B85 ) ( 23 ). After surface staining, the cells were fixed, permeabilized, and intracellularly stained for NGAL (ab224264; Abcam, Cambridge, UK), which was conjugated to metal isotope 159Tb, using the Maxpar X8 Antibody Labeling Kit, 159Tb-4 RXN (Standard BioTools, see Supplementary Table 2, Supplementary Digital Content 1, http://links.lww.com/CTG/B85 ).…”

“…Samples with more than 100,000 events were used for analysis. PBMC populations and subsets were gated based on phenotypic markers of each population (see Supplementary Table 3, Supplementary Digital Content 1, http://links.lww.com/CTG/B85 ) ( 23 ). Differences in NGAL + of PBMC populations were calculated as the number of cells positive for NGAL within an immune population divided by the number of live PBMCs positive for NGAL.…”

A Cancer Prevention and Treatment Opportunity

“…The FcRn is found in MDSCs in pancreatic cancer monocytes. MDSCs and DCs are elevated in pancreatic cancer patients compared to non-cancer donors [46]. They can be targeted through AFPR and/or FcRn by AFP-toxin drugs.…”

Alpha-Fetoprotein: A Revolutionary Anti-Cancer Drug

“…Interestingly, FcRn is elevated in MDSCs, monocyte, and DCs in pancreatic cancer ductal adenocarcinoma. 142 Cancer can be as simple as pregnancy prevention.…”