TY  - JOUR
AU  - Lattanzi, Chiara
AU  - Bianchetto-Aguilera, Francisco
AU  - Donini, Marta
AU  - Pettinella, Francesca
AU  - Caveggion, Elena
AU  - Castellucci, Monica
AU  - Gasperini, Sara
AU  - Mariotti, Barbara
AU  - Signoretto, Ilaria
AU  - Cantini, Maurizio
AU  - Pilotto, Sara
AU  - Belluomini, Lorenzo
AU  - Tecchio, Cristina
AU  - Bazzoni, Flavia
AU  - Brandau, Sven
AU  - Tamassia, Nicola
AU  - Cassatella, Marco A
AU  - Scapini, Patrizia
TI  - Uncovering common transcriptional features shared by mature peripheral blood PMN-MDSCs and tumor-infiltrating neutrophils in humans.
JO  - OncoImmunology
VL  - 14
IS  - 1
SN  - 2162-4011
CY  - Abingdon
PB  - Taylor & Franics
M1  - DKFZ-2025-01338
SP  - 2521396
PY  - 2025
AB  - Human polymorphonuclear-myeloid-derived suppressor cells (PMN-MDSCs) consist of circulating low-density neutrophils (LDNs) characterized by the ability to inhibit T-cell responses. In previous studies, we demonstrated that the mature fraction of PMN-MDSCs (i.e. mPMN-MDSCs) exerts more potent immunosuppressive functions than its immature counterpart. More recently, we defined a specific gene signature of mPMN-MDSCs from cancer patients and G-CSF-treated donors (GDs) by bulk RNA sequencing (RNA-seq) experiments. In this study, by performing single-cell RNA-seq (scRNA-seq) experiments of circulating mPMN-MDSCs from non-small cell lung cancer (NSCLC) patients, we identified a major scRNA-seq cell cluster (arbitrarily named NSCLC c6) specifically displaying immunosuppressive and protumor transcriptomic features. Then, by analyzing publicly available scRNA-seq datasets from human tumor-associated neutrophils (TANs), we uncovered three TAN clusters (arbitrarily named TAN c6-c8) that were found to share with NSCLC c6 several common genes and transcription factor (TF) regulons associated with response to hypoxia, positive regulation of angiogenesis, and metabolic reprogramming. Furthermore, by performing scRNA-seq experiments of GD mPMN-MDSCs, we uncovered four scRNA-seq cell clusters (arbitrarily named GD c4-c7) that were enriched for the same genes and pathways characterizing NSCLC c6 and TAN c6-c8 cells. Altogether, these data uncover that human circulating mPMN-MDSCs and TANs from different cancer types share scRNA-seq cell clusters with transcriptomic similarities, supporting the notion that they might be strictly related.
KW  - Humans
KW  - Neutrophils: immunology
KW  - Neutrophils: metabolism
KW  - Neutrophils: pathology
KW  - Carcinoma, Non-Small-Cell Lung: genetics
KW  - Carcinoma, Non-Small-Cell Lung: immunology
KW  - Carcinoma, Non-Small-Cell Lung: pathology
KW  - Lung Neoplasms: genetics
KW  - Lung Neoplasms: immunology
KW  - Lung Neoplasms: pathology
KW  - Myeloid-Derived Suppressor Cells: metabolism
KW  - Myeloid-Derived Suppressor Cells: immunology
KW  - Myeloid-Derived Suppressor Cells: pathology
KW  - Single-Cell Analysis
KW  - Gene Expression Regulation, Neoplastic
KW  - Transcriptome
KW  - Gene Expression Profiling
KW  - Tumor Microenvironment: immunology
KW  - G-CSF (Other)
KW  - Neutrophils (Other)
KW  - PMN-MDSCs (Other)
KW  - TANs (Other)
KW  - scRNA-seq (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:40590753
C2  - pmc:PMC12218443
DO  - DOI:10.1080/2162402X.2025.2521396
UR  - https://inrepo02.dkfz.de/record/302798
ER  -