TAAs are presented along with the major histocompatibility complex (MHC) I or II by specialized antigen-presenting cells (APCs) that bind with T-cell receptors (TCRs). These TAAs are recognized by the immune system, and T cells can be stimulated in response to cellular presentation of TAAs. Transformed tumor cells express tumor-associated antigens (TAAs) that are not seen on normal cells. The immune system has an important role in recognizing and eliminating tumors. This review summarizes the current clinical information of IMC, its postulated mechanism of injury, endoscopic features, and the management strategies that are currently advocated. As a result, addressing GI irAEs has become a major clinical issue for physicians and patients alike. The incidence of IMC ranges from 0.3% to 7% and may be associated with other immune-related adverse events (irAEs). While representing a remarkable breakthrough in the treatment of several advanced malignancies, several ICI-related adverse events that affect multiple body systems (Table (Table1 1)have been recognized, including immune-mediated colitis (IMC) and enteritis. Indeed, ICIs have become the standard of care for a number of cancers and resulted in the awarding of the 2018 Nobel Prize in Physiology or Medicine to Allison and Honjo in recognition of their contribution to the discovery of ICIs. To date there are 7 approved checkpoint inhibitors that target 3 main checkpoints, including cytotoxic T-lymphocyte associated protein 4 (CTLA-4 ipilimumab and tremelimumab), programmed cell death receptor 1 (PD-1 pembrolizumab and nivolumab), and programmed death ligand 1 (PD-L1 atezolizumab, avelumab, and durvalumab). Such seminal work culminated with the Food and Drug Administration (FDA) approving the first ICI for use in metastatic melanoma in 2011. A study on tumors in animal models provided proof of concept that an antibody was successful in blocking the cytotoxic T-lymphocyte antigen 4 (CTLA-4). This discovery was soon followed by the first ever reported human tumor antigen recognized by T-cells. The pivotal change in the history of immune checkpoint inhibitors (ICIs) began with the discovery of the T-cell receptor by Allison et al in the early 1980s. Towards the late 1800s, sarcoma regression was seen after injecting tumors with heat-inactivated bacteria known as “Coley’s Toxins”. ![]() ![]() In the early 19 th century, Busch and Fehleisen, both noted that infecting tumors with erysipelas resulted in tumor regression. Scientists have long experimented with the idea that the immune system holds the potential to fight not only infections but also malignancy. While in grade 4 colitis, the immunotherapy is permanently discontinued, the decision is controversial in grade 3 colitis. Recently vedolizumab has been found to be efficacious in steroid and infliximab refractory cases. About one third to two thirds of patients are steroid refractory and benefit from infliximab. Corticosteroids are recommended for grade 2 or more severe colitis while holding the immunotherapy. Endoscopically and histologically there is a significant overlap between IMC and inflammatory bowel disease, however more neutrophilic inflammation without chronic inflammation is usually present in IMC. ![]() The incidence of immune-mediated colitis (IMC) ranges from 1%-25% depending on the type of ICI and if used in combination. However, many immune-related adverse events have also been described which mainly occurs as the immune system becomes less suppressed, affecting various organs including the gastrointestinal tract and causing diarrhea and colitis. ICIs have revolutionized the treatment of a variety of malignancies. Immune checkpoint inhibitors (ICIs) are monoclonal antibodies that target down-regulators of the anti-cancer immune response: Cytotoxic T-lymphocyte antigen-4, programmed cell death protein-1, and its ligand programmed death-ligand 1.
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