Arf1-mediated lipid metabolism sustains cancer cells and its ablation induces anti-tumor immune responses in mice

Guohao Wang, Junji Xu, Jiangsha Zhao, Weiqin Yin, Dayong Liu, WanJun Chen and Steven X. Hou ()
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Guohao Wang: National Cancer Institute at Frederick, National Institutes of Health
Junji Xu: National Institutes of Health
Jiangsha Zhao: National Cancer Institute at Frederick, National Institutes of Health
Weiqin Yin: National Cancer Institute at Frederick, National Institutes of Health
Dayong Liu: National Cancer Institute at Frederick, National Institutes of Health
WanJun Chen: National Institutes of Health
Steven X. Hou: National Cancer Institute at Frederick, National Institutes of Health

Nature Communications, 2020, vol. 11, issue 1, 1-16

Abstract: Abstract Cancer stem cells (CSCs) may be responsible for treatment resistance, tumor metastasis, and disease recurrence. Here we demonstrate that the Arf1-mediated lipid metabolism sustains cells enriched with CSCs and its ablation induces anti-tumor immune responses in mice. Notably, Arf1 ablation in cancer cells induces mitochondrial defects, endoplasmic-reticulum stress, and the release of damage-associated molecular patterns (DAMPs), which recruit and activate dendritic cells (DCs) at tumor sites. The activated immune system finally elicits antitumor immune surveillance by stimulating T-cell infiltration and activation. Furthermore, TCGA data analysis shows an inverse correlation between Arf1 expression and T-cell infiltration and activation along with patient survival in various human cancers. Our results reveal that Arf1-pathway knockdown not only kills CSCs but also elicits a tumor-specific immune response that converts dying CSCs into a therapeutic vaccine, leading to durable benefits.

Date: 2020
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DOI: 10.1038/s41467-019-14046-9

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