التفاصيل البيبلوغرافية
العنوان: |
Highly multiplexed spatial analysis identifies tissue-resident memory T cells as drivers of ulcerative and immune checkpoint inhibitor colitis |
المؤلفون: |
van Eijs, Mick J.M., ter Linde, José J.M., Baars, Matthijs J.D., Amini, Mojtaba, Laclé, Miangela M., Brand, Eelco C., Delemarre, Eveline M., Drylewicz, Julia, Nierkens, Stefan, Verheijden, Rik J., Oldenburg, Bas, Vercoulen, Yvonne, Suijkerbuijk, Karijn P.M., van Wijk, Femke |
المساهمون: |
Cancer, MS Medische Oncologie, CTI Van Wijk, Infection & Immunity, MS MDL 1, CMM, CMM Groep Vercoulen, Pathologie Pathologen staf, CTI Eijkelkamp, CTI Bont, CTI Computational Immunology Core, CTI Research, Child Health |
سنة النشر: |
2023 |
مصطلحات موضوعية: |
Components of the immune system, Health sciences, Immunology, Proteomics, General, Journal Article |
الوصف: |
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(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+ TRM cells as potentially targetable drivers of ICI colitis. |
نوع الوثيقة: |
article in journal/newspaper |
وصف الملف: |
application/pdf |
اللغة: |
English |
تدمد: |
2589-0042 |
العلاقة: |
https://dspace.library.uu.nl/handle/1874/450094Test |
الإتاحة: |
https://dspace.library.uu.nl/handle/1874/450094Test |
حقوق: |
info:eu-repo/semantics/OpenAccess |
رقم الانضمام: |
edsbas.27069C42 |
قاعدة البيانات: |
BASE |