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Updated: Jun 4, 2026
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Mapping Infant Immunity with Minimal Input: Integrative Single-Cell and Multiomic Profiling
Published on: April 3, 2026
Identification of immunosuppressive neutrophils using multi-omics: why functional testing remains key
Fleur van Oosterom1,2, Angela A F Gankema1,2, Felipe Rojas-Rodriguez1,2
1Department of Molecular Hematology, Sanquin Research, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, Netherlands.
Frontiers in Immunology
|June 3, 2026
Summary
Polymorphonuclear neutrophils (PMNs) can act as myeloid-derived suppressor cells (MDSCs) in tumors. Further single-cell techniques are needed to precisely define these immunosuppressive neutrophil subsets for cancer therapy.
Area of Science:
- Immunology
- Oncology
- Cell Biology
Background:
- Polymorphonuclear neutrophils (PMNs) are innate immune cells with potential myeloid-derived suppressor cell (MDSC) activity, particularly within the tumor microenvironment.
- While activated neutrophils exhibit suppressive functions, certain subsets like low-density neutrophils may possess intrinsic MDSC activity.
- Single-cell RNA sequencing (scRNAseq) offers a novel approach to investigate neutrophil heterogeneity and immunosuppressive functions.
Purpose of the Study:
- To explore the potential of PMNs as MDSCs and characterize distinct neutrophil subsets within tumors.
- To investigate the utility of scRNAseq in identifying immunosuppressive neutrophils for targeted cancer therapies.
- To address the current limitations in immunophenotypic characterization and functional validation of PMN-MDSCs.
Main Methods:
- Review and analysis of existing studies on PMN-MDSCs and neutrophil subsets.
- Exploration of single-cell RNA sequencing (scRNAseq) as a tool for neutrophil subtyping.
- Discussion of the need for functional testing and advanced single-cell techniques like proteomics.
Main Results:
- scRNAseq has advanced the study of neutrophil heterogeneity but has not yet yielded a clear immunophenotypic definition of PMN-MDSCs.
- A discrepancy exists between RNA abundance, protein expression, and functional activity in neutrophils, highlighting the complexity of defining subsets.
- Clinical relevance and functional validation of identified neutrophil subsets remain a significant challenge.
Conclusions:
- Defining functional neutrophil subsets, particularly PMN-MDSCs, requires further development of single-cell technologies beyond scRNAseq.
- Integrating techniques like proteomics with scRNAseq is crucial for accurately characterizing neutrophil subsets and their plasticity.
- Advancements in these areas are essential for developing effective targeted immunotherapies for cancer patients.
