Back to Search
Start Over
Deterministic reprogramming of neutrophils within tumors.
- Source :
-
Science (New York, N.Y.) [Science] 2024 Jan 12; Vol. 383 (6679), pp. eadf6493. Date of Electronic Publication: 2024 Jan 12. - Publication Year :
- 2024
-
Abstract
- Neutrophils are increasingly recognized as key players in the tumor immune response and are associated with poor clinical outcomes. Despite recent advances characterizing the diversity of neutrophil states in cancer, common trajectories and mechanisms governing the ontogeny and relationship between these neutrophil states remain undefined. Here, we demonstrate that immature and mature neutrophils that enter tumors undergo irreversible epigenetic, transcriptional, and proteomic modifications to converge into a distinct, terminally differentiated dcTRAIL-R1 <superscript>+</superscript> state. Reprogrammed dcTRAIL-R1 <superscript>+</superscript> neutrophils predominantly localize to a glycolytic and hypoxic niche at the tumor core and exert pro-angiogenic function that favors tumor growth. We found similar trajectories in neutrophils across multiple tumor types and in humans, suggesting that targeting this program may provide a means of enhancing certain cancer immunotherapies.
- Subjects :
- Humans
Proteomics
Receptors, TNF-Related Apoptosis-Inducing Ligand immunology
Epigenesis, Genetic
Hypoxia
Transcription, Genetic
Neoplasms blood supply
Neoplasms immunology
Neutrophils immunology
Cellular Reprogramming genetics
Cellular Reprogramming immunology
Neovascularization, Pathologic genetics
Neovascularization, Pathologic immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1095-9203
- Volume :
- 383
- Issue :
- 6679
- Database :
- MEDLINE
- Journal :
- Science (New York, N.Y.)
- Publication Type :
- Academic Journal
- Accession number :
- 38207030
- Full Text :
- https://doi.org/10.1126/science.adf6493