TY  - JOUR
A1  - Olesch, Catherine
A1  - Brunn, David
A1  - Aktay-Cetin, Öznur
A1  - Sirait-Fischer, Evelyn Nicole Joy
A1  - Pullamsetti, Soni
A1  - Grimminger, Friedrich
A1  - Seeger, Werner
A1  - Brüne, Bernhard
A1  - Weigert, Andreas
A1  - Savai, Rajkumar
T1  - Picturing of the lung tumor cellular composition by multispectral flow cytometry
T2  - Frontiers in immunology
N2  - The lung tumor microenvironment plays a critical role in the tumorigenesis and metastasis of lung cancer, resulting from the crosstalk between cancer cells and microenvironmental cells. Therefore, comprehensive identification and characterization of cell populations in the complex lung structure is crucial for development of novel targeted anti-cancer therapies. Here, a hierarchical clustering approach with multispectral flow cytometry was established to delineate the cellular landscape of murine lungs under steady-state and cancer conditions. Fluorochromes were used multiple times to be able to measure 24 cell surface markers with only 13 detectors, yielding a broad picture for whole-lung phenotyping. Primary and metastatic murine lung tumor models were included to detect major cell populations in the lung, and to identify alterations to the distribution patterns in these models. In the primary tumor models, major altered populations included CD324+ epithelial cells, alveolar macrophages, dendritic cells, and blood and lymph endothelial cells. The number of fibroblasts, vascular smooth muscle cells, monocytes (Ly6C+ and Ly6C–) and neutrophils were elevated in metastatic models of lung cancer. Thus, the proposed clustering approach is a promising method to resolve cell populations from complex organs in detail even with basic flow cytometers.
KW  - lung cancer
KW  - tumor microenvironment
KW  - lung tumor heterogeneity
KW  - multispectral flow cytometry
KW  - hierarchical clustering
Y1  - 2022
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/74309
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-743092
SN  - 1664-3224
N1  - This work was supported by Deutsche Krebshilfe (70112451), Deutsche Forschungsgemeinschaft (FOR 2438, TP8, SFB 1039, TP B04 and B06, GRK 2336, TP1 and 6, SFB 1213 TPA01, A05, and A10), Wilhelm-Sander Foundation (2019.082.01) and the LOEWE Center Frankfurt Cancer Institute (FCI) funded by the Hessen State Ministry for Higher Education, Research and the Arts [III L 5 - 519/03/03.001 - (0015)]. Further support was received from the Max Planck Society, Cardio-Pulmonary Institute (CPI), the German Center for Lung Research (DZL) and European Research Council (ERC) Consolidator Grant (#866051 to SSP).
VL  - 13
IS  - art. 827719
SP  - 1
EP  - 13
PB  - Frontiers Media
CY  - Lausanne
ER  -