Author:
Manna Subhakankha,Sehn Maximilian,Cardoso da Silva Danielle,Wiese Jakob J.,Heldt Claudia,Plumbom Izabela,Conrad Thomas,Husemann Cora C.,Kleo Karsten,Derêzanin Lorena,Dony Violaine,Farahani Saeed K.,Weiss Franziska,Branchi Federica,Kühl Anja A.,Schallenberg Simon,Weiner January,Elezkurtaj Sefer,Weixler Benjamin,Gröne Jörn,Siegmund Britta,Hummel Michael,Schumann Michael
Abstract
AbstractPatients with ulcerative colitis (UC) and Crohn’s disease (CD) face a lifelong risk of developing colitis-associated carcinoma (CAC). Current insights into CAC development originate from murine CAC models, while human CAC studies primarily focus on mutational analysis of patient samples. Although the mutational landscape reveals distinct patterns and frequencies compared to colorectal cancer, it falls short in elucidating the inflammatory mechanisms of CAC development. Consequently, we adopted a multi-omics approach to unravel CAC carcinogenesis from an immunological perspective. Our data revealed a robust upregulation ofSPP1gene in CAC at both RNA and protein levels, expressed byCD68+macrophages. In vitro OPN stimulation demonstrated no direct effect on intestinal epithelial organoids. However, the mutually exclusive spatial location ofSPP1/OPN+macrophages andCD8+T cells suggests a crucial indirect role ofSPP1/OPNin mediating an immunosuppressive tumour microenvironment.
Publisher
Cold Spring Harbor Laboratory