The Role of the Immune System in IBD-Associated Colorectal Cancer: From Pro to Anti-Tumorigenic Mechanisms

Abstract

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.

Development of an immune-related gene prognostic risk model and identification of an Immune infiltration signature in the tumor microenvironment of colon cancer

“…The differences in drug sensitivity and prognosis re ect that colon cancer is highly heterogeneous in the TME. Generally, speci c genetic and epigenetic alterations in colon cancer affect the composition of TME [8, 10,11]. The development of colon cancer is inextricably linked to dysregulated TME.…”

Development of an immune-related gene prognostic risk model and identification of an Immune infiltration signature in the tumor microenvironment of colon cancer

“…The differences in drug sensitivity and prognosis re ect that colon cancer is highly heterogeneous in the TME. Generally, speci c genetic and epigenetic alterations in colon cancer affect the composition of TME [13,15,16]. The development of colon cancer is inextricably linked to dysregulated TME.…”

Molecular Mechanisms of Tumor Immunomodulation in the Microenvironment of Colorectal Cancer

“…Both the tumor characteristics and the patient conditions affect the composition of the TME, subsequently dictating disease progression, responsiveness to cancer treatments and survival prognosis. Indeed, the primary tumor’s specific genetic and epigenetic alterations, its localization (i.e., ascending, transverse or descending colon, or rectum) and the hosting organs in case of metastasis strongly impact the composition of the TME [ 19 , 20 , 21 ]. Furthermore, the patient’s genetic pre-disposition, co-morbidities, bowel pre-conditions (e.g., inflammatory bowel diseases) or lifestyle (e.g., diet, physical activities, smoking) similarly alter the TME [ 22 ].…”