RT Journal Article SR Electronic T1 Immunoglobulin-like transcript 2 (ILT2) is a biomarker of therapeutic response to oncolytic immunotherapy with vaccinia viruses JF Journal for ImmunoTherapy of Cancer JO J Immunother Cancer FD BMJ Publishing Group Ltd SP 1 DO 10.1186/2051-1426-2-1 VO 2 IS 1 A1 Andrew Zloza A1 Dae Won Kim A1 Seunghee Kim-Schulze A1 Michael C Jagoda A1 Vladia Monsurro A1 Francesco M Marincola A1 Howard L Kaufman YR 2014 UL http://jitc.bmj.com/content/2/1/1.abstract AB Background Oncolytic viruses represent a novel form of cancer immunotherapy. Vaccinia viruses encoding human T cell co-stimulatory molecules have demonstrated clinical activity in phase I clinical trials in patients with advanced melanoma. However, predictive biomarkers of therapeutic response have not yet been identified.Methods A customized microarray was performed to identify changes in peripheral blood mononuclear cell (PBMC) gene expression upon exposure to recombinant oncolytic vaccinia viruses. Up-regulated and down-regulated genes were identified and selected for further analysis using PBMC samples from normal donors and oncolytic virus-treated patients before and after viral injection. Quantitative PCR and flow cytometry of defined T cell subsets was performed to evaluate expression patterns and clinical correlations.Results The microarray identified 301 genes that were up-regulated and 960 genes that were down-regulated in T cells after exposure to oncolytic vaccinia virus. The B7.1 gene was highly up-regulated and the immunoglobulin-like transcript 2 (ILT2) gene was highly down-regulated by vaccinia-B7.1, which was consistent with the known inverse regulation of these two genes. We observed an inverse association between ILT2 expression in the tumor microenvironment and clinical response and further identified ILT2 as a marker of regulatory CD4+ and suppressor CD8+ T cell responses and whose down-regulation was predictive of therapeutic responses in patients treated with oncolytic virus immunotherapy.Conclusions ILT2 is a new putative biomarker of T cell and clinical response in patients treated with oncolytic vaccinia virus immunotherapy. Further confirmation of ILT2 as a biomarker requires prospective validation in a larger series of clinical trials.Abbreviations:ILT2Immunoglobulin-like transcript 2PBMCPeripheral blood mononuclear cellrV-B7.1Recombinant vaccinia viruses encoding human B7.1rV-TRICOMRecombinant vaccinia viruses encoding a triad of T cell co-stimulatory molecules including B7.1, ICAM-1, and LFA-3rVRecombinant vaccinia virusesTregCD4+FoxP3+ regulatory T cellTsCD8+FoxP3+ suppressor T cell.