Immune checkpoint inhibitor-mediated colitis in gastrointestinal malignancies and inflammatory bowel disease

Abstract

Immune checkpoint inhibitors (ICI) have markedly changed the landscape of cancer therapy. By re-invigorating the immune system against tumors, ICI provide novel therapeutic options for a broad variety of malignancies, including many gastrointestinal (GI) cancers. However, these therapies can also induce autoimmune-like side effects in healthy tissue across the body. One of the most common of these side effects is ICI-mediated colitis and diarrhea (IMC). Here, we review the incidence and risk of IMC in ICI therapy, with a focus on what is known regarding IMC in patients with GI malignancies. We also discuss data available on the use of ICI and risk of IMC in patients with pre-existing inflammatory bowel disease, as these patients may have increased risk of IMC due to their underlying intestinal pathology.

The colitis may be microscopic, but the diarrhea is not: update on the treatment of microscopic colitis and immune checkpoint inhibitor colitis

“…This higher incidence of diarrhea was also noted when a PD-1/PDL1 and a TKI were used in combination [49 && ]. Other predictors of ICPi colitis include the type of malignancy, race, sex, age, lack of vitamin D supplementation, and recent pneumococcal pneumonia vaccine [53].…”

“…Other predictors of ICPi colitis include the type of malignancy, race, sex, age, lack of vitamin D supplementation, and recent pneumococcal pneumonia vaccine [53].…”

Checkpoint Inhibitors and the Gut

“…This involves uncontrolled T-cell and B-cell proliferation in multiple organs, leading to a widespread multi-organ inflammatory condition, typically involving dermatitis, nephritis, hepatitis, and colitis. ICI also interacts with interleukin-17 production [31]. Mice studies showed that the administration of PDL-1 antibodies can dampen IL-17 concentration in the colon, which may explain why PDL-1 therapies have fewer colonic irAEs compared to CTLA-4 [31][32][33].…”

“…ICI also interacts with interleukin-17 production [31]. Mice studies showed that the administration of PDL-1 antibodies can dampen IL-17 concentration in the colon, which may explain why PDL-1 therapies have fewer colonic irAEs compared to CTLA-4 [31][32][33]. Changes in the population of resident CD8+ T-cells in the colon were also speculated to enhance inflammatory response [34].…”

Check this out: treatment paradigms in immune-checkpoint inhibitor colitis

“…There is even a consideration that a certain level of diarrhea has a favorable outcome and is a proxy way to see therapy effectiveness. In one study of patients with metastatic melanoma, those who develop irAEs including colitis were associated with improved OS and progression-free survival (PFS) [24 ▪ ].…”