Neutrophil reprogramming in tumors; plus Red Queen, Orbis platforms and more

Researchers from Singapore’s Agency for Science Technology and Research (A*STAR), Shanghai Jiao Tong University and elsewhere published an article in Science showing mature neutrophils that enter tumors undergo irreversible epigenetic, transcriptional and proteomic modifications. The authors used single-cell RNA sequencing and ATACseq, which reveals chromatin packaging and other factors affecting gene expression, to determine neutrophil states in the tumor microenvironment in a mouse model of pancreatic cancer. The terminally differentiated neutrophils expressed dcTRAIL-R1 and VEGF-A, localized to a unique hypoxic-glycolytic niche near the tumor core, and promoted pro-angiogenic function to support tumor growth.

“Our findings thus demonstrate how short-lived effector cells such as neutrophils effectively tailor their functions to accommodate tissue requirements, highlighting the untapped possibilities of targeting the local neutrophil response as immunotherapy,” the authors wrote...