Expression of tumor-associated B7-H1 prior to treatment seemed to correlate with the favorable clinical response to anti-PD-1 therapy in a small patient cohort [30], suggesting the potential use of tumor

B7-H1 expression as a biomarker. Nevertheless, several important issues remain to be addressed in future studies. B7-H2 is known to be upregulated on APCs and peripheral tissues upon stimulation by TLR ligands or proinflammatory cytokines. As a result, the mechanism underlying B7-H2 downregulation on leukemia cells upon co-culture with activated T cells needs to be further elucidated. It also remains to be validated whether similar adaptive immune phenotype changes will occur in vivo in AML cells from different patients, as observed in leukemia cell lines in vitro, or in only a percentage of the cancer patients. Most importantly, the results of the clinical response NVP-BGJ398 and phenotypic changes noted in the current ongoing anti-PD-1 trials in leukemia should provide invaluable information about the dynamic interactions of a fluid tumor and host immune system, and help

inform the strategy to be used to overcome tumor adaptive evasion. We like to thank Beth Cadugan for editing the manuscript. This work is supported by NIH grant CA142779, CA121974, CA16359 and CA97085. “
“Appendicitis followed by appendectomy (AA) at a young age protects against AZD8055 molecular weight inflammatory bowel disease (IBD). Using a novel murine appendicitis model, we showed that AA protected against subsequent experimental colitis. To delineate genes/pathways involved in this protection, AA was performed and samples harvested from the most distal colon. RNA was extracted from four individual colonic samples per group (AA group and double-laparotomy control group) and each sample microarray analysed followed by gene-set enrichment analysis (GSEA). The gene-expression study was validated by quantitative reverse transcription–polymerase chain reaction (RT–PCR) of 14 selected genes across the immunological spectrum. Distal colonic expression of 266 gene-sets was up-regulated significantly in AA group

samples (false discovery rates < 1%; P-value < 0·001). Time–course RT–PCR experiments involving the 14 genes displayed down-regulation over 28 days. The IBD-associated genes Metalloexopeptidase tnfsf10, SLC22A5, C3, ccr5, irgm, ptger4 and ccl20 were modulated in AA mice 3 days after surgery. Many key immunological and cellular function-associated gene-sets involved in the protective effect of AA in experimental colitis were identified. The down-regulation of 14 selected genes over 28 days after surgery indicates activation, repression or de-repression of these genes leading to downstream AA-conferred anti-colitis protection. Further analysis of these genes, profiles and biological pathways may assist in developing better therapeutic strategies in the management of intractable IBD.