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Article source: Medicine Cube Pro
Author: Heart Fruit
In the past 10 years, there has been a major development in cancer immunotherapy research.
In fact, small metabolites from immune cells are also abundant in some tissues, and many metabolites may have yet-to-be-understood signaling and immune target potential
On November 3, in a study published in Nature, a research team from Yokohama Institute of Physics and Chemistry and Kyoto University found that B cells can release gamma-aminobutyric acid metabolite (GABA, a well-known neurotransmitter molecule).
First, after the researchers challenged normal wild-type (WT) mice with antigen, they found that the levels of about 200 metabolites were significantly different in lymph nodes (a type of immune cell-rich tissue) near the immune site, especially with Glutamate (the upstream molecule that secretes GABA) pathway system activates related metabolites
Pathway analysis of metabolites with significantly different abundances in lymph nodes of normal WT mice; levels of metabolites and GABA in lymph nodes of immunodeficient mice (Source: Nature)
When B cells detect antigenic fragments through the B cell receptor (BCR), they synthesize and secrete GABA
B cells in mice and humans synthesize and secrete GABA (Source: Nature)
In a mouse model of colon cancer, administration of GABA to B cell-deficient mice reduced CD8 T cell infiltration in tumors and reduced cytotoxicity and production of inflammatory molecules
In addition to suppressing CD8 T cell responses, GABA also has a role in tumor-associated macrophages
Source: Nature
Finally, the researchers created mice whose B cells did not express GAD67 (ie, GABA-deficient)
Source: Nature
Collectively, this study demonstrates that GABA secreted by B cells can activate anti-inflammatory macrophages and inhibit the antitumor response of CD8 T cells through GABAA receptors
References:
[1] Zhang, B.
[2] GABA molecules made by B cells can dampen antitumour responses (Source: Nature)
