Immune-Mediated Inflammatory Diseases and Cancer - a dangerous liaison

Abstract

Patients with Immune-Mediated Inflammatory Diseases (IMIDs) are known to have an elevated risk of developing cancer, but the exact causative factors remain subject to ongoing debate. This narrative review aims to present the available evidence concerning the intricate relationship between these two conditions. Environmental influences and genetic predisposition lead to a dysregulated immune response resulting in chronic inflammation, which is crucial in the pathogenesis of IMIDs and oncogenic processes. Mechanisms such as the inflammatory microenvironment, aberrant intercellular communication due to abnormal cytokine levels, excessive reparative responses, and pathological angiogenesis are involved. The chronic immunosuppression resulting from IMIDs treatments further adds to the complexity of the pathogenic scenario. In conclusion, this review highlights critical gaps in the current literature, suggesting potential avenues for future research. The intricate interplay between IMIDs and cancer necessitates more investigation to deepen our understanding and improve patient management.

Keywords: Immune-Mediated Inflammatory Diseases; biologic therapy; immune dysregulation; immunosuppression; inflammation; malignancy.

Figure 1

Genetic and environmental factors contribute to the etiopathogenesis of IMID. The environmental factors that promote IMIDs are the same as those that cause cancer. The boxes on the right summarize the mechanisms involved. Everything converges on a significant dysregulation of the immune system, with inflammation being a key event. For details see the text. Image created with BioRender.com.

Figure 2

A schematic diagram illustrating the molecular mechanisms in sporadic (CRC) and IBD-related colorectal cancer. CRC arises from the accumulation of mutations in oncogenes and tumor suppressor genes, driving the progression from single preneoplastic cells to adenoma and ultimately to carcinoma. In contrast, IBD-related colorectal cancer is driven by chronic inflammation, which leads to the production of proinflammatory cytokines and the buildup of reactive oxygen and nitrogen species, promoting genomic aberrations and instability. This process results in mutations in oncogenes and tumor suppressor genes. Mutations in p53 lead to low-grade dysplastic mucosa, with subsequent mutations in KRAS contributing to the progression from low-grade to high-grade dysplasia. Finally, mutations in the APC gene culminate in the development of cancer. Image created with BioRender.com.