CD200 is overexpressed in the pancreatic tumor microenvironment and predictive of overall survival
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Date
2024-03
Authors
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Publisher
Springer Nature
Abstract
Background: Pancreatic ductal adenocarcinoma (PDAC) has a five-year survival rate of 13% 1. A fibrotic and immunosuppressive tumor microenvironment (TME), difficulty of early detection, and resistance to chemotherapy all contribute to the poor survival 2. CD200 is a glycoprotein that interacts with its receptor CD200R, which is expressed on myeloid cells, and elicits an immunosuppressive response 3. Our laboratory was the first to report that CD200 is overexpressed in PDAC and promotes immune suppression in preclinical animal models 4. The objective of this research is to further characterize CD200 expression in PDAC. We hypothesized that CD200 expression is overexpressed in the pancreatic TME and that soluble CD200 (sCD200) expression in PDAC is associated with worse overall survival.
Methods: We performed multiplex immunofluorescence (IF) on tissue microarrays containing pancreatic tumors (n= 127), cancer adjacent tissue (n= 27), and normal pancreatic tissue (n=18) and analyzed the expression of CD200 on tumor, stromal, and immune populations. Additionally, we assessed CD200 expression on circulating immune populations from patients with PDAC using cytometry by time of flight (CyTOF). CD200 can also be cleaved by matrix metalloproteases (MMPs) into functional sCD200 5, and we investigated whether this occurs in patients with PDAC. We performed ELISA to measure the serum levels of sCD200 in untreated metastatic PDAC patients. We defined patients with high serum sCD200 as having levels higher than the median (283 pg/mL).
Results: We observed that CD200 expression was significantly upregulated on tumor and stromal populations in the pancreatic TME compared to cancer adjacent and normal pancreatic tissue. We identified a significant increase in CD200 surface expression on monocytes, plasmacytoid DCs, and monocytic myeloid-derived suppressor cells (MDSCs) on PBMC from PDAC patients compared to healthy donor controls. Patients that had high serum levels of sCD200 (n=15) had significantly worse overall survival and progression-free survival than patients that had low serum levels of sCD200 (n=44).
Conclusions: We showed that CD200 is upregulated by tumor and stromal populations in the pancreatic TME and by circulating myeloid populations. Additionally, higher concentrations of sCD200 in the plasma of metastatic PDAC correlated with worse survival outcomes.
Significance: This work highlights the importance of CD200 expression in patients with PDAC and provides rationale for the design of novel therapeutic approaches for targeting this protein in patients.
Description
Poster Division: Biological & Health Sciences: 2nd Place (The Ohio State University Edward F. Hayes Advanced Research Forum)
Keywords
pancreatic cancer, CD200, tumor microenvironment, Overall Survival
Citation
Published version: Wedig, J., Jasani, S., Mukherjee, D. et al. CD200 is overexpressed in the pancreatic tumor microenvironment and predictive of overall survival. Cancer Immunol Immunother 73, 96 (2024). https://doi.org/10.1007/s00262-024-03678-6