Gut microbiota in humanized microbiome mice shape naïve immune patterns

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Presentation Time: 03:15 PM - 04:30 PM
Poster Board Number: B208
Abstract ID: 7412

Presenting Author:
Alexis N Cox-Holmes , Graduate Research Assistant at Univ. of Alabama, Birmingham, Heersink Sch. of Med.

Abstract:

In mouse models of glioblastoma (GBM), immunotherapy is effective in increasing survival, but this is not the case in clinical trials. To address this issue, we utilized a novel humanized microbiome (HuM) mouse model created by transplanting fecal matter from healthy human donors into gnotobiotic mice. Our previous work found that in the GL261 model of GBM, HuM mouse lines were classified as either responders or nonresponders to anti-PD-1 therapy. In this report, we sought to determine the immune differences in the naïve (tumor-free) HuM mice to uncover the mechanisms by which the gut microbiota dictate the efficacy of immunotherapy in GBM. In the gut-draining lymph nodes of naïve HuM mice, responders had a higher frequency of CD45⁺ immune cells and CD3⁺CD4⁺CD8⁺ double positive T (DP T) cells, as well as a lower frequency of Tregs than nonresponders. In cervical lymph nodes, which drain the brain, there was a higher frequency of DP T cells and RORgt⁺FoxP3⁺ Tregs, the latter traditionally thought to be gut microbiota specific Tregs, in naïve responders compared to nonresponders. The brains of responders had a higher frequency of CD45⁺ cells and microglia than nonresponders, suggesting that the responder HuM mice had a larger immune cell population in the brain. These findings show that differences in the microbiota of the HuM mice affect the baseline immune landscape in numerous immune organs as well as the brain.