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Metabolic-immune microenvironment crosstalk mediating ICI resistance in MASH-HCC.

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Trends in endocrinology and metabolism: TEM 2026 Vol.37(3) p. 262-276
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Ju Y, Xu K, Chen X, Wu T, Yuan Y

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As a pivotal immunotherapy modality, immune checkpoint inhibitors (ICIs) have demonstrated significant clinical efficacy in a variety of malignant tumors, including viral hepatocellular carcinoma (HCC

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APA Ju Y, Xu K, et al. (2026). Metabolic-immune microenvironment crosstalk mediating ICI resistance in MASH-HCC.. Trends in endocrinology and metabolism: TEM, 37(3), 262-276. https://doi.org/10.1016/j.tem.2025.06.008
MLA Ju Y, et al.. "Metabolic-immune microenvironment crosstalk mediating ICI resistance in MASH-HCC.." Trends in endocrinology and metabolism: TEM, vol. 37, no. 3, 2026, pp. 262-276.
PMID 40695685 ↗

Abstract

As a pivotal immunotherapy modality, immune checkpoint inhibitors (ICIs) have demonstrated significant clinical efficacy in a variety of malignant tumors, including viral hepatocellular carcinoma (HCC). However, metabolic-associated steatohepatitis-related hepatocellular carcinoma (MASH-HCC) is significantly resistant to ICI, its metabolic-immune crosstalk mechanisms have not been systematically defined, and methods to improve the efficacy of ICI in this context are lacking. Thus, here we elucidate the microenvironmental features of MASH-HCC, focusing on tumor metabolic-immune crosstalk mechanisms such as metabolic reprogramming, metabolic stress, fibrosis, and the gut-liver axis, and summarize clinical and preclinical studies currently assessing whether metabolic drugs may help with overcoming ICI resistance and improving clinical efficacy against MASH-HCC.

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