When Neutrophils Do Not Die: Senescence as a New Axis of Tumor Immunosuppression

In this issue of Cancer Discovery, Chen and colleagues leverage single-cell RNA sequencing of neutrophils in the tumor microenvironment of colorectal cancer liver metastases to characterize neutrophil heterogeneity within the metastatic immune landscape. They show that the glucose-deprived metastatic microenvironment drives BHLHE40 upregulation in neutrophils, inducing a senescent tumor-associated neutrophil (TAN) population, TAN1, that actively promotes angiogenesis and excludes CD8+ T cells from the tumor, thereby supporting tumor growth and survival. See related article by Chen et al., p. 2130.