“Deterministic reprogramming of neutrophils within tumors” (2024), by Melissa Shu Feng Ng et al. Immunology and Microbiology research paper. Original abstract below, unchanged. A free PDF is available.

Deterministic reprogramming of neutrophils within tumors

Melissa Shu Feng Ng, Immanuel Kwok, Leonard Tan et al. · January 11, 2024 · Immunology and Microbiology

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 + state. Reprogrammed dcTRAIL-R1 + 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.

Free PDF DOI: 10.1126/science.adf6493