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The intestinal flora is a collection of large numbers of bacteria in the human intestine
.
It is estimated that each person’s digestive tract carries approximately 100 trillion bacteria from thousands of species
In recent years, the intestinal flora has been a research hotspot
.
More and more discoveries indicate that the intestinal flora is not only of core importance for digestion, but also affects a large number of bodily functions
Recent studies have shown that the intestinal flora can directly affect the effect of cancer immunotherapy
.
However, there is very little research on the role of intestinal flora metabolites in regulating cancer immunotherapy
July 1, 2021,German research team at the University of Nature Communications journal published a report entitled: Microbial catena alberghiera Short-fatty Acids modulate CD8 + T and the Cell Responses Improve adoptive Immunotherapy for Cancer research paper
.
This study is the first experiment to prove that the two microbial metabolites of valeric acid and butyric acid enhance the anti-tumor activity of immune cells through metabolism and epigenetic reprogramming, confirming that valeric acid and butyric acid have optimal effects in cancer immunotherapy
.
Symbiotic bacteria containing broad-spectrum enzymes can produce a variety of small molecules that can be used for therapeutic intervention
.
The research team observed that the low-abundance human symbiont M.
They then treated CD8 + T cells with supernatant containing valeric acid and butyric acid from M.
massiliensis to observe their functional changes
.
The results showed that valeric acid and butyric acid produced by M.
Short-chain fatty acids (SCFA) are known inhibitors of histone deacetylase (HDAC) that can modulate the fate of eukaryotic cells through epigenetic methods
.
The research team compared the histone deacetylase (HDAC) inhibitory activity of the supernatants from 16 species of human symbiotic bacteria
.
They found that butyrate and valerate inhibit HDAC class I enzymes, reprogram CD8 + T cells, and increase the production of pro-inflammatory and cytotoxic molecules
Further experimental results show that treatment with fatty acid valerate enhances the ability of tumor-specific T cells against solid tumor models
.
Normal T cells are "blind" to tumor cells to a large extent, while CAR-T cells can recognize specific target antigens on the tumor surface and kill cancer cells
.
Therefore, in order to further develop potential treatment strategies, the research team studied the impact of short-chain fatty acids (SCFA) on CAR-T cell therapy
They found that valerate treatment enhanced the therapeutic effect of CAR-T cell therapy on pancreatic cancer, proving the potential of using valeric acid and butyric acid to optimize CAR-T cell generation to enhance CAR-T cell adoptive transfer.
In summary, the study revealed two microbial metabolites valeric acid and butyric acid that can be used to enhance cellular anti-tumor immunity, and demonstrated two potential anti-tumor therapies: one is the use of valeric acid and butyric acid to optimize cytotoxic T cells The other is to transfer the bacterial population that produces these short-chain fatty acids (SCFA) to patients receiving adoptive cell therapy
Original source:
Original source:Luu, M.
, Riester, Z.
, Baldrich, A.
et al.
Microbial short-chain fatty acids modulate CD8+ T cell responses and improve adoptive immunotherapy for cancer.
Nat Commun 12, 4077 (2021).
https://doi.
org/10.
1038/s41467-021-24331-1.
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