The two faces of neutrophils in tumor biology

(Vienna, 26.03.2024) Neutrophils are the most common white blood cells and an important component of the immune system. They help in the defense against pathogens and in the healing of injuries. They are also suspected to play a role in tumor development. A team from St. Anna Children’s Cancer Research Institute (CCRI) has now compared the maturation process of neutrophils in several organisms to unravel developmental similarities. The findings help to better understand the role of neutrophil maturation in tumor development. The study was recently published in the renowned journal Nature Communications.

Recently, the pro- and anti-tumor roles of neutrophils, cells of the innate immune system, have become a focus of cancer research. There appear to be subpopulations of these cells that interact with tumors in very different ways. Scientists suspect that the function in the tumor context is related to the degree of maturity of these immune cells. “We want to investigate this in the zebrafish model in the long term,” says Martin Distel, PhD, head of the Zebrafish platform Austria for preclinical drug screening (ZANDR) at St. Anna Children’s Cancer Research Institute (CCRI) and one of the last authors of the recently published study.

Researchers published a study about neutrophils in Nature Communications.
f.l. Mohammed Shoeb, Martin Distel, Florian Halbritter, Stefanie Kirchberger

Marking neutrophils

Stefanie Kirchberger, PhD, one of the first authors of the paper, investigated the maturation of neutrophil immune cells in zebrafish larvae. She used two different fluorescent markers for this purpose. While one marker lights up in all neutrophils, the second marker only shows mature neutrophils. The team was therefore able to draw conclusions about the degree of maturity of the observed cells, she explains. When these mature neutrophils encounter mutated cells, they enter into closer contact with them than immature neutrophils.

Comparison with human immune cells

By analyzing the genes expressed during neutrophil maturation in zebrafish and comparing them with data from other models from various previously published studies, the group of Principal Investigator Florian Halbritter, PhD, was able to summarize and compare gene activity patterns.

Mohamed Shoeb, PhD student in this group: “The activity patterns we identified represent groups of genes that are activated at certain stages of neutrophil development in our zebrafish model. To our surprise, we found that the same patterns are also common during neutrophil development in humans and mice.” Halbritter adds: “This enabled us to assign the developmental stages of neutrophils in the three organisms and to better understand the biological process.”

Bone marrow of neuroblastoma patients

In this phase, the researchers combined their data with analyses of the bone marrow of neuroblastoma patients. These data were contributed by the tumor biology group of Sabine Taschner-Mandl, PhD, at the St. Anna Children’s Cancer Research Institute. The samples from bone marrow biopsies of neuroblastoma patients with infiltrating tumor cells were compared with samples without tumor cells. This made it possible to determine the degree of maturity of the neutrophils in the vicinity of the tumor cells by using the newly defined maturity signature. The effects of differently mature neutrophils on tumorigenesis can now be further investigated and results can be more easily transferred from model organisms to humans on the basis of the knowledge gained in this study.


Kirchberger S, Shoeb MR, Lazic D, Wenninger-Weinzierl A, Fischer K, Shaw LE, Nogueira F, Rifatbegovic F, Bozsaky E, Ladenstein R, Bodenmiller B, Lion T, Traver D, Farlik M, Schöfer C, Taschner-Mandl S, Halbritter F, Distel M. Comparative transcriptomics coupled to developmental grading via transgenic zebrafish reporter strains identifies conserved features in neutrophil maturation. Nat Commun. 2024 Feb 27;15(1):1792.
doi: 10.1038/s41467-024-45802-1