Systemic iron sequestration restricts the intratumoral CD8 + T cell landscape in pancreas cancer
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Systemic iron sequestration occurs frequently in cancer due to inflammation-driven expression of the iron-regulatory hormone hepcidin. The impact of systemic iron availability on tumoral immunity is unclear. Here, we show that elevated serum hepcidin is associated with reduced survival and decreased intratumoral CD8 + T cells in patients with pancreas cancer. While hepcidin is not induced in murine tumor models, administration of a hepcidin mimetic phenocopies the T-cell-depleted tumor microenvironment seen in patients. Mechanistically, chronic antigen-driven mitochondrial dysfunction disrupts iron metabolism and selectively depletes high avidity CD8 + T cells during iron restriction. These findings establish a direct link between hepcidin-mediated iron sequestration and tumoral immunity and nominate systemic iron dysregulation as a therapeutic target to enhance anti-tumoral CD8 + T cell responses.
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Can restoring iron availability improve T-cell fitness and tumor control? That is an important therapeutic question for future studies. Read the preprint: www.biorxiv.org/content/10.6...
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In our latest work, led by Josh Schoenfeld, we explore one of the great enigmas of cancer biology: how systemic iron sequestration promotes tumor progression. www.biorxiv.org/content/10.6... 🧵
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Systemic iron sequestration restricts the intratumoral CD8+ T cell landscape in pancreas cancer https://www.biorxiv.org/content/10.64898/2026.09.21.753167v1
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Systemic iron sequestration restricts the intratumoral CD8+ T cell landscape in pancreas cancer https://www.biorxiv.org/content/10.64898/2026.09.21.753167v1
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