Host metadherin coordinates hepatic lipid metabolism and CD8(+) T cell immunity to promote tumor progression.

Loss of host MTDH in hepatocytes and CD8+ T cells enhances antitumor immunity and suppresses tumor growth and metastasis in mouse models.

• Why it matters: Understanding how tumor-organ communication influences immune suppression and metabolism is crucial for developing effective cancer therapies. This work addresses the gap in knowledge about systemic tumor-liver crosstalk and its impact on antitumor immunity.
• What they did: Researchers used Mtdh knockout mice to investigate tumor-liver interactions, analyzing effects on immune function and metabolism, and examined how tumor-derived extracellular vesicles activate Kupffer cells to influence hepatic lipid oxidation.
• The result: Mtdh loss restores hepatic lipid catabolism, reduces systemic lipid levels, and boosts mitochondrial reprogramming in CD8+ T cells, which, combined with anti-PD-1 therapy, enhances antitumor responses.