Surface CD52, CD84, and PTGER2 mark mature PMN-MDSCs from cancer patients and G-CSF-treated donors
Francesca Pettinella1, Barbara Mariotti1, Chiara Lattanzi1
1Section of General Pathology, Department of Medicine, University of Verona, 37134 Verona, Italy.
Abstract:
Precise molecular characterization of circulating polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) is hampered by their mixed composition of mature and immature cells and lack of specific markers. Here, we focus on mature CD66b+CD10+CD16+CD11b+ PMN-MDSCs (mPMN-MDSCs) from either cancer patients or healthy donors receiving G-CSF for stem cell mobilization (GDs). By RNA sequencing (RNA-seq) experiments, we report the identification of a distinct gene signature shared by the different mPMN-MDSC populations under investigation, also validated in mPMN-MDSCs from GDs and tumor-associated neutrophils (TANs) by single-cell RNA-seq (scRNA-seq) experiments. Analysis of such a gene signature uncovers a specific transcriptional program associated with mPMN-MDSC differentiation and allows us to identify that, in patients with either solid or hematologic tumors and in GDs, CD52, CD84, and prostaglandin E receptor 2 (PTGER2) represent potential mPMN-MDSC-associated markers. Altogether, our findings indicate that mature PMN-MDSCs distinctively undergo specific reprogramming during differentiation and lay the groundwork for selective immunomonitoring, and eventually targeting, of mature PMN-MDSCs.
Insights
Researchers identified a unique gene signature in mature polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs). This discovery reveals potential markers (CD52, CD84, PTGER2) for targeting these cells in cancer patients and healthy donors.
Area of Science:
- Immunology
- Molecular Biology
- Cancer Research
Background:
- Circulating polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) are crucial immune regulators but challenging to characterize due to cellular heterogeneity and lack of specific markers.
- Mature PMN-MDSCs (mPMN-MDSCs) play a significant role in immune suppression, particularly in cancer and during G-CSF treatment.
Purpose of the Study:
- To identify a distinct molecular signature for mature PMN-MDSCs (mPMN-MDSCs).
- To discover novel cell surface markers associated with mPMN-MDSCs for potential immunomonitoring and therapeutic targeting.
Main Methods:
- RNA sequencing (RNA-seq) was employed to analyze gene expression profiles of mPMN-MDSCs from cancer patients and healthy donors receiving G-CSF.
- Single-cell RNA sequencing (scRNA-seq) was used to validate the identified gene signature in mPMN-MDSCs and tumor-associated neutrophils (TANs).
Main Results:
- A unique gene signature was identified in mPMN-MDSCs across different populations, indicating specific transcriptional reprogramming during differentiation.
- CD52, CD84, and prostaglandin E receptor 2 (PTGER2) were identified as potential cell surface markers associated with mPMN-MDSCs.
- The findings were validated in mPMN-MDSCs from healthy donors and tumor-associated neutrophils (TANs).
Conclusions:
- Mature PMN-MDSCs exhibit distinct differentiation-associated transcriptional programs.
- CD52, CD84, and PTGER2 represent promising targets for the selective immunomonitoring and potential therapeutic targeting of mPMN-MDSCs in cancer and other conditions.
