Multiplex spatial omics reveals changes in immune-epithelial crosstalk during inflammation and dysplasia development in chronic IBD patients.

Patients with long-standing inflammatory bowel disease (IBD) face an increased risk of developing colitis-associated cancer (CAC). Although IBD-induced prolonged inflammation seems to be involved in CAC pathogenesis, the specific molecular changes that contribute remain unknown. Here, we applied digital spatial RNA profiling, RNAscope, and imaging mass cytometry to examine paired uninflamed, inflamed, and early dysplastic mucosa of patients with IBD. We observed robust type 3 (IL-17) responses during inflammation, accompanied by elevated JAK-STAT signaling and phosphorylated STAT3 (P-STAT3) levels, with both inflamed and dysplastic mucosa displaying immune cell activation. Higher stromal P-STAT3 was detected in uninflamed and inflamed mucosa of patients who eventually developed dysplasia. CD8a ⁺ T cells did not infiltrate inflamed or dysplastic epithelial regions in these patients, while control patients showed elevated CD8a in inflamed mucosa. Our study reveals distinct inflammatory patterns throughout CAC development, marked by an activated IL-17 pathway, engaged STAT3, and diminished cytotoxic T cell infiltration.
Competing Interests: B.O. received research grants from AbbVie, Celltrion, Ferring, Takeda, Galapagos, and Pfizer and is a member of the advisory boards of Cablon, Pfizer, BMS, Janssen, MSD, Takeda, and Galapagos. Y.V. received a Public Private Partnership grant from Health Holland (#TKI2017), with TigaTx BV and received a research grant from Galapagos.
(© 2024 The Author(s).)