Patients with inflammatory bowel disease (IBD) have increased incidence of colorectal cancer (CRC). IBD-associated cancer follows a well-characterized sequence of intestinal epithelial changes, in which genetic mutations and molecular aberrations play a key role. IBD-associated cancer develops against a background of chronic inflammation and pro-inflammatory immune cells, and their products contribute to cancer development and progression. In recent years, the effect of the immunosuppressive microenvironment in cancer development and progression has gained more attention, mainly because of the unprecedented anti-tumor effects of immune checkpoint inhibitors in selected groups of patients. Even though IBD-associated cancer develops in the background of chronic inflammation which is associated with activation of endogenous anti-inflammatory or suppressive mechanisms, the potential role of an immunosuppressive microenvironment in these cancers is largely unknown. In this review, we outline the role of the immune system in promoting cancer development in chronic inflammatory diseases such as IBD, with a specific focus on the anti-inflammatory mechanisms and suppressive immune cells that may play a role in IBD-associated tumorigenesis.

Immune-mediated inflammatory diseases (IMIDs) are characterized by chronic systemic inflammation and multi-organ involvement. Fibrosis formation in IMIDs can cause tissue destruction and subsequently organ malfunction. Fibroblast activation protein inhibitor positron emission tomography/computed tomography (FAPi PET/CT) represents a novel imaging technique that holds great potential to visualize in vivo fibrosis. We here provide an overview of available evidence on FAPi PET/CT imaging to visualize fibrosis in various IMIDs, including interstitial lung diseases, immunoglobulin G4-related diseases, cardiovascular diseases, kidney diseases, and gastrointestinal diseases. FAPi PET/CT imaging demonstrates high sensitivity in detecting early fibrosis, correlating with disease severity, across different IMIDs, showing superiority compared to conventional imaging modalities. Although FAPi PET/CT might be a useful tool to assess fibrosis formation, thereby aiding in grading disease severity and staging, future studies should include larger sample sizes in a broad variety of IMIDs with emphasis on the optimization of imaging protocols to further validate its diagnostic value.

Immune-mediated inflammatory diseases (IMIDs) are characterized by chronic systemic inflammation and multiorgan involvement. Fibrosis formation in IMIDs can cause tissue destruction and subsequently organ malfunction. Fibroblast activation protein inhibitor positron emission tomography/computed tomography (FAPi PET/CT) represents a novel imaging technique that holds great potential to visualize in vivo fibrosis. We here provide an overview of available evidence on FAPi PET/CT imaging to visualize fibrosis in var-ious IMIDs, including interstitial lung diseases, Immunoglobulin G4-related diseases, cardiovascular diseases, kidney diseases and gastrointestinal diseases. FAPi PET/CT imaging demonstrates high sensitivity in detecting early fibrosis, correlating with dis-ease severity, across different IMIDs, showing superiority compared to conventional imaging modalities. Although FAPi PET/CT might be a useful tool to assess fibrosis formation, thereby aiding in grading disease severity and staging, future studies should include larger sample sizes in a broad variety of IMIDs with emphasis on the optimiza-tion of imaging protocols to further validate its diagnostic value.

Intestinal fibrosis is a major complication of Crohn's disease (CD), for which no effective antifibrotic therapies are currently available, partly due to an incomplete understanding of its underlying mechanisms. Emerging evidence suggests that metabolic reprogramming of stromal cells may contribute to fibrogenesis. This Y‐ECCO literature review summarises the study by Zhou et al., which investigated metabolic alterations in intestinal fibrosis using multi‐omics approaches. Paired stricturing and non‐stricturing intestinal specimens from patients with CD were analysed using metabolomics, single‐cell transcriptomics, and spatial transcriptomics, complemented by functional validation in primary human intestinal myofibroblasts and murine models. The study identified activation of the pentose phosphate pathway (PPP) in fibrotic intestinal tissue, predominantly driven by fibroblasts. Xylulose‐5‐phosphate (Xu5P), a key PPP metabolite, was enriched in stricturing disease, correlated with fibrosis severity, and promoted fibroblast activation in vitro and in vivo. Mechanistically, Xu5P production was regulated by xylulokinase (XYLB) and negatively controlled by circular RNA circPLCE1, which was downregulated in fibrotic tissue. Loss of circPLCE1 enhanced PPP activity and fibrotic remodelling, defining a circPLCE1–XYLB–Xu5P axis. These findings identify metabolic reprogramming as a key driver of intestinal fibrosis in CD and suggest potential diagnostic and therapeutic targets, although clinical translation of PPP‐targeting strategies remains to be established.