The evolving landscape of transcriptomic technologies tailored for neutrophil research.
ABSTRACT
Tumor neutrophils exhibit marked phenotypic plasticity and can play dual roles in tumor biology, encompassing both tumor-promoting and tumor-suppressive activities. Single-cell RNA sequencing (scRNA-seq) enables transcriptomic profiling of tumor neutrophils at single-cell resolution, whereas spatial transcriptomics (ST) addresses key limitations of scRNA-seq by preserving the spatial context of cells within intact tissue, thereby minimizing cell loss and maintaining native tissue architecture. As ST technology continues to advance, it offers increasingly comprehensive insights into the regulatory mechanisms of tumor neutrophils within the tumor microenvironment (TME). In this review, we first summarize recent technological advancements in ST. We then discuss neutrophil detection across various cancer types, highlighting key differences and challenges in neutrophil research across studies and malignancies. Furthermore, we outline recommendations for sequencing strategies and sample processing to optimize the study of tumor neutrophils. Finally, we highlight that integrating ST with multi-omics approaches offers a promising avenue to advance our understanding of tumor neutrophil biology and to identify more precise biomarkers for targeted therapies.