Immune checkpoint inhibitors(ICIs) are monoclonal antibodies that target downregulators of the anti-cancer immune response: Cytotoxic T-lymphocyte antigen-4, programmed cell death protein-1, and its ligand programmed ...Immune checkpoint inhibitors(ICIs) are monoclonal antibodies that target downregulators of the anti-cancer immune response: Cytotoxic T-lymphocyte antigen-4, programmed cell death protein-1, and its ligand programmed death-ligand 1.ICIs have revolutionized the treatment of a variety of malignancies. 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. The incidence of immune-mediated colitis(IMC) ranges from 1%-25% depending on the type of ICI and if used in combination. 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. Corticosteroids are recommended for grade 2 or more severe colitis while holding the immunotherapy. About one third to two thirds of patients are steroid refractory and benefit from infliximab. Recently vedolizumab has been found to be efficacious in steroid and infliximab refractory cases. While in grade 4 colitis, the immunotherapy is permanently discontinued, the decision is controversial in grade 3 colitis.展开更多
Colorectal cancer(CRC)remains one of the major causes of death worldwide,despite steady improvement in early detection and overall survival over the past decade.Current treatment paradigms,with chemotherapy and biolog...Colorectal cancer(CRC)remains one of the major causes of death worldwide,despite steady improvement in early detection and overall survival over the past decade.Current treatment paradigms,with chemotherapy and biologics,appear to have reached their maximum benefit.Immunotherapy,especially with checkpoint inhibitors,has shown considerable clinical benefit in various cancers,including mismatch-repair-deficient CRC.This has led to the planning and initiation of several clinical trials evaluating novel immunotherapy agents—as single agents,combinations and in conjunction with chemotherapy—in patients with CRC.This article reviews biological and preclinical data for checkpoint inhibitors and discusses various immunotherapy trials in CRC,as well as current efforts in CRC immunotherapy.展开更多
文摘Immune checkpoint inhibitors(ICIs) are monoclonal antibodies that target downregulators of the anti-cancer immune response: Cytotoxic T-lymphocyte antigen-4, programmed cell death protein-1, and its ligand programmed death-ligand 1.ICIs have revolutionized the treatment of a variety of malignancies. 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. The incidence of immune-mediated colitis(IMC) ranges from 1%-25% depending on the type of ICI and if used in combination. 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. Corticosteroids are recommended for grade 2 or more severe colitis while holding the immunotherapy. About one third to two thirds of patients are steroid refractory and benefit from infliximab. Recently vedolizumab has been found to be efficacious in steroid and infliximab refractory cases. While in grade 4 colitis, the immunotherapy is permanently discontinued, the decision is controversial in grade 3 colitis.
文摘Colorectal cancer(CRC)remains one of the major causes of death worldwide,despite steady improvement in early detection and overall survival over the past decade.Current treatment paradigms,with chemotherapy and biologics,appear to have reached their maximum benefit.Immunotherapy,especially with checkpoint inhibitors,has shown considerable clinical benefit in various cancers,including mismatch-repair-deficient CRC.This has led to the planning and initiation of several clinical trials evaluating novel immunotherapy agents—as single agents,combinations and in conjunction with chemotherapy—in patients with CRC.This article reviews biological and preclinical data for checkpoint inhibitors and discusses various immunotherapy trials in CRC,as well as current efforts in CRC immunotherapy.
