Microbiota-Derived Short-Chain Fatty Acids Boost Antitumoral Natural Killer Cell Activity

微生物衍生的短链脂肪酸增强抗肿瘤自然杀伤细胞活性

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作者:Marina Pérez, Berta Buey, Pilar Corral, David Giraldos, Eva Latorre

Background

The intestinal microbiota can regulate numerous host functions, including the immune response. Through fermentation, the microbiota produces and releases microbial metabolites such as short-chain fatty acids (SCFAs), which can affect host homeostasis. There is growing evidence that the gut microbiome can have a major impact on cancer. Specific gut microbial composition and metabolites are associated with tumor status in the host. However, their effects on the antitumor response have scarcely been investigated. Natural killer (NK) cells play an important role in antitumor immunity due to their ability to directly identify and eliminate tumor cells.

Conclusions

Our results indicate, for the first time, the enormous potential of SCFAs in regulating antitumoral NK cell defense, where modulation of the SCFAs' production could play a fundamental role in cancer immunotherapy.

Methods

The aim of this study was to investigate the effects of SCFAs on antitumoral NK cell activity, using NK-92 cell line.

Results

Here, we describe how SCFAs can boost antitumoral NK cell activity. The SCFAs induced the release of NK extracellular vesicles and reduced the secretion of the anti-inflammatory cytokine IL-10. The SCFAs also increased the cytotoxicity of the NK cells against multiple myeloma cells. Conclusions: Our results indicate, for the first time, the enormous potential of SCFAs in regulating antitumoral NK cell defense, where modulation of the SCFAs' production could play a fundamental role in cancer immunotherapy.

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