The composition of the intestinal microbiota influences the development of inflammatory disorders.,However, associating inflammatory diseases with specific microbial members of the microbiota is challenging, because clinically detectable inflammation and its treatment can alter the microbiota's composition.,Immunologic checkpoint blockade with ipilimumab, a monoclonal antibody that blocks cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) signalling, is associated with new-onset, immune-mediated colitis.,Here we conduct a prospective study of patients with metastatic melanoma undergoing ipilimumab treatment and correlate the pre-inflammation faecal microbiota and microbiome composition with subsequent colitis development.,We demonstrate that increased representation of bacteria belonging to the Bacteroidetes phylum is correlated with resistance to the development of checkpoint-blockade-induced colitis.,Furthermore, a paucity of genetic pathways involved in polyamine transport and B vitamin biosynthesis is associated with an increased risk of colitis.,Identification of these biomarkers may enable interventions to reduce the risk of inflammatory complications following cancer immunotherapy.,A subset of cancer patients treated with immune checkpoint blockade develops colitis.,Here the authors show that lower abundance of Bacteroidetes and vitamin B biosynthetic modules in fecal samples of melanoma patients can predict their susceptibility to colitis following anti-CTLA-4 treatment.
Ipilimumab, an antibody that enhances T-cell activation, may augment immunogenicity of tumor cells that are injured by radiation therapy.,We hypothesized that patients with melanoma brain metastasis treated with both ipilimumab and radiotherapy would have improved overall survival, and that the sequence of treatments may affect disease control in the brain.,We analyzed the clinical and radiographic records of melanoma patients with brain metastases who were treated with whole brain radiation therapy or stereotactic radiosurgery between 2005 and 2012.,The hazard ratios for survival were estimated to assess outcomes as a function of ipilimumab use and radiation type.,Seventy patients were identified, 33 of whom received ipilimumab and 37 who did not.,The patients who received ipilimumab had a censored median survival of 18.3 months (95% confidence interval 8.1-25.5), compared with 5.3 months (95% confidence interval 4.0-7.6) for patients who did not receive ipilimumab.,Ipilimumab and stereotactic radiosurgery were each significant predictors of improved overall survival (hazard ratio = 0.43 and 0.45, with P = 0.005 and 0.008, respectively).,Four of 10 evaluable patients (40.0%) who received ipilimumab prior to radiotherapy demonstrated a partial response to radiotherapy, compared with two of 22 evaluable patients (9.1%) who did not receive ipilimumab.,Ipilimumab is associated with a significantly reduced risk of death in patients with melanoma brain metastases who underwent radiotherapy, and this finding supports the need for multimodality therapy to optimize patient outcomes.,Prospective studies are needed and are underway.