Phenotyping EMT and MET cellular states in lung cancer patient liquid biopsies at a personalized level using mass cytometry

• Published in: Scientific reports Vol. 13; no. 1; pp. 21781 - 11
• Main Authors: Karacosta, Loukia G., Pancirer, Danny, Preiss, Jordan S., Benson, Jalen A., Trope, Winston, Shrager, Joseph B., Sung, Arthur Wai, Neal, Joel W., Bendall, Sean C., Wakelee, Heather, Plevritis, Sylvia K.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 08-12-2023; Nature Publishing Group; Nature Portfolio
• Subjects: 631/114; 631/114/1305; 631/114/2404; 631/114/663; 631/1647/2067; 631/553; 631/67; 631/67/1612; 631/67/1857; 631/67/2329; 692/53; Biopsy; Carcinoma, Non-Small-Cell Lung - pathology; Cytokeratin; Cytometry; Epithelial-Mesenchymal Transition - physiology; Feasibility studies; Humanities and Social Sciences; Humans; Immunotherapy; Liquid Biopsy; Lung cancer; Lung Neoplasms - pathology; multidisciplinary; Myeloid cells; Non-small cell lung carcinoma; Patients; Phenotyping; Pleural Effusion; Pleural Effusion, Malignant - drug therapy; Proteomics; Science; Science (multidisciplinary); Small cell lung carcinoma
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-023-46458-5

Malignant pleural effusions (MPEs) can be utilized as liquid biopsy for phenotyping malignant cells and for precision immunotherapy, yet MPEs are inadequately studied at the single-cell proteomic level. Here we leverage mass cytometry to interrogate immune and epithelial cellular profiles of primary tumors and pleural effusions (PEs) from early and late-stage non-small cell lung cancer (NSCLC) patients, with the goal of assessing epithelial-mesenchymal transition (EMT) and mesenchymal-epithelial transition (MET) states in patient specimens. By using the EMT–MET reference map PHENOSTAMP, we observe a variety of EMT states in cytokeratin positive (CK+) cells, and report for the first time MET-enriched CK+ cells in MPEs. We show that these states may be relevant to disease stage and therapy response. Furthermore, we found that the fraction of CD33+ myeloid cells in PEs was positively correlated to the fraction of CK+ cells. Longitudinal analysis of MPEs drawn 2 months apart from a patient undergoing therapy, revealed that CK+ cells acquired heterogeneous EMT features during treatment. We present this work as a feasibility study that justifies deeper characterization of EMT and MET states in malignant cells found in PEs as a promising clinical platform to better evaluate disease progression and treatment response at a personalized level.