High‐dimensional single cell mapping of cerium distribution in the lung immune microenvironment of an active smoker

• Published in: Cytometry. Part B, Clinical cytometry Vol. 94; no. 6; pp. 941 - 945
• Main Authors: Rahman, Adeeb H., Lavin, Yonit, Kobayashi, Soma, Leader, Andrew, Merad, Miriam
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01-11-2018
• Subjects: Adenocarcinoma; Alveoli; Antibodies; Biological properties; Biological samples; cancer; Cell suspensions; Cerium; CyTOF; Cytometry; Dimensional analysis; Heterogeneity; immune monitoring; Immune system; immunology; immunophenotyping; Isotopes; lung; Lung cancer; macrophage; Macrophages; Mapping; mass cytometry; Mass spectrometry; Mass spectroscopy; microenvironment; Phagocytosis; Rare earth elements; Smoking; Surgery; Tissues; Toxicology; Tumors; lung; microenvironment; cerium; immunophenotyping; macrophage; cancer; immune monitoring; mass cytometry; CyTOF; immunology
• ISSN: 1552-4949; 1552-4957
• DOI: 10.1002/cyto.b.21545

Background
Mass cytometry leverages inductively coupled mass spectrometry to perform high dimensional single cell analyses using antibodies tagged with rare earth isotopes that are considered to be largely absent in biological samples. We have recently noted an unusual exception to this rule while analyzing tissue samples from patients undergoing surgical resection for early stage lung cancer, and here we present a detailed cytometric characterization of cerium in a clinical patient sample.
Methods
We performed a CyTOF analysis on cell suspensions derived from matched blood, tumor lesion, and non‐involved lung tissue from an active smoker undergoing surgical resection for early stage lung adenocarcinoma. The samples were stained with a 31‐parameter antibody panel to allow a detailed characterization of the cellular heterogeneity of the samples. The data were visualized using viSNE, major immune subsets were identified based on canonical marker expression patterns, and single cell cerium levels were evaluated across each of these defined subsets.
Results
High dimensional immune cell mapping revealed that high levels of cerium were specifically associated with a phenotypically distinct subset of lung macrophages that were most prevalent in noninvolved lung tissue, whereas tumor associated macrophages showed relatively lower levels of cerium. We hypothesize that these findings reflect alveolar macrophage phagocytosis of inhaled cerium derived from cigarette flint lighters.
Conclusions
These results demonstrate the first high‐dimensional single cell characterization of environmental metal exposure associated with smoking, and offer a demonstration of the unique potential for applying mass cytometry to the field of environmental toxicology. © 2017 International Clinical Cytometry Society