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Highly multiplexed spatial analysis identifies tissue-resident memory T cells as drivers of ulcerative and immune checkpoint inhibitor colitis. | LitMetric

AI Article Synopsis

  • - Colitis linked to immune checkpoint inhibitors (ICI) resembles inflammatory bowel disease, but we lack a full understanding of its mechanisms, complicating treatment options.
  • - By using imaging mass cytometry (IMC), researchers examined immune cell behavior in ICI colitis compared to ulcerative colitis, revealing that CD8 T cells are more abundant in ICI-induced colitis.
  • - The study found that activated CD8 T cells are key players in the inflammation seen in ICI colitis, indicating they might be potential targets for future therapies.

Article Abstract

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 intra-epithelial CD8 T cells are significantly more abundant (and numerically 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 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 cells as potentially targetable drivers of ICI colitis.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10520880PMC
http://dx.doi.org/10.1016/j.isci.2023.107891DOI Listing

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