Claudin-7 deficiency induces metabolic reprogramming of neutrophils in the colorectal cancer microenvironment.

ABSTRACT: Neutrophils are integral components of the bone marrow and stromal cell network. They express the immune checkpoint molecule PD-L1 and can induce T cell exhaustion, thereby promoting immunosuppression. In this study, we investigated whether tumor-derived Cldn7 deficiency could recruit polymorphonuclear neutrophils (PMNs), induce their metabolic reprogramming, and consequently drive their transition toward a pro-tumor phenotype, leading to the establishment of an immunosuppressive tumor microenvironment (TME). Using single-cell RNA sequencing, clinical sample validation, and both in vivo and in vitro experiments, we found that Cldn7 deficiency in colorectal cancer (CRC) results in a tumor microenvironment characterized by significantly increased infiltration of CD11b⁺ Ly6G⁺ neutrophils. Thi

SUBMITTER: Liang X 

PROVIDER: S-EPMC12533015 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature