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- W4366998408 abstract "Summary Colitis is a prevalent adverse event associated with immune checkpoint inhibitor (ICI) therapy with similarities to inflammatory bowel disease. Incomplete mechanistic understanding of ICI-colitis curtails evidence-based treatment. Given the often-overlooked connection between tissue architecture and mucosal immune cell function, we here applied imaging mass cytometry (IMC) to gain spatial proteomic insight in ICI-colitis in comparison to ulcerative colitis (UC). Using a cell segmentation pipeline that simultaneously utilizes high-resolution nuclear imaging and high-multiplexity IMC, we show that CD8 + T cells are significantly more abundant (and dominant) in anti-PD-1 +/-anti-CTLA-4-induced colitis compared to anti-CTLA-4-induced colitis and UC. We identified activated, cycling CD8 + tissue-resident memory T (T RM ) cells at the lamina propria-epithelial interface as drivers of cytotoxicity in ICI-colitis and UC. Moreover, we found that combined ICI-induced colitis featured highest granzyme B levels both in tissue and serum. Together, these data reinforce CD8 + T RM cells as potentially targetable drivers of ICI-colitis." @default.
- W4366998408 created "2023-04-27" @default.
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- W4366998408 date "2023-04-25" @default.
- W4366998408 modified "2023-10-06" @default.
- W4366998408 title "Highly multiplexed spatial analysis identifies tissue-resident memory T cells as drivers of ulcerative and immune checkpoint inhibitor induced colitis" @default.
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- W4366998408 doi "https://doi.org/10.1101/2023.04.25.23289056" @default.
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