Blockade of various immune targets such as cytotoxic T-lymphocyte antigen-4 and Programmed cell death leads to immune-mediated tumor regression and immune-related adverse events, predominantly gastrointestinal events including diarrhea and colitis. The current review is done to understand the underlying mechanism of action and to identify potential biomarkers that could help in the prediction and management of gastrointestinal immune-related adverse events. Histological assessment of bowel biopsies and assessment of serologic markers of inflammatory bowel disease and colitis secondary to immune mediated antibodies are reviewed. Ipilimumab causes dysregulation of gastrointestinal mucosal immunity, which can be evidenced by altered antibody levels to enteric flora and inflammatory cell infiltration into gastrointestinal mucosa associated with diarrhea and clinical evidence of colitis. The pattern of drug induced antibody titers to microbial flora and the histological features and location of the inflammation were distinct from classic inflammatory bowel disease. Although classic inflammatory bowel disease and immune mediated antibodies related gastrointestinal toxicity are both immune mediated, the pattern of biomarkers and histological features suggests that the later may be a distinct clinicopathologic entity.