Tumor cell death by ferroptosis contributes to an immunosuppressive tumor microenvironment in syngeneic murine models of cancer.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is characterized by profound metabolic rewiring and a strongly immunosuppressive tumor microenvironment, both of which contribute to poor therapeutic responses. Immunogenic cell death (ICD) represents a potential strategy to overcome immune suppression by coupling tumor cell death to anti-tumor immune activation. Here, we investigated whether targeting amino acid metabolism in PDAC can induce ICD and promote tumor immunity. Through a focused metabolic screen in a panel of syngeneic mouse cancer cell lines, we identified cysteine restriction as a robust inducer of multiple damage-associated molecular patterns (DAMPs) in vitro, hallmark features of ICD. In addition to driving DAMPs, cystine-deprived tumor cells also promoted dendritic cell phagocytosis

SUBMITTER: Mbah NE 

PROVIDER: S-EPMC12803264 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature