Immunoglobulin-like transcript 2 ILT2 is a biomarker of therapeutic response to oncolytic immunotherapy with vaccinia virusesReport as inadecuate




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Journal for ImmunoTherapy of Cancer

, 2:1

Immunotherapy Biomarkers

Abstract

BackgroundOncolytic 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.

MethodsA 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.

ResultsThe 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.

ConclusionsILT2 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.

KeywordsImmunoglobulin-like transcript 2 Biomarker Vaccinia Oncolytic virus Immunotherapy T cells Cancer vaccines AbbreviationsILT2Immunoglobulin-like transcript 2

PBMCPeripheral blood mononuclear cell

rV-B7.1Recombinant vaccinia viruses encoding human B7.1

rV-TRICOMRecombinant vaccinia viruses encoding a triad of T cell co-stimulatory molecules including B7.1, ICAM-1, and LFA-3

rVRecombinant vaccinia viruses

TregCD4+FoxP3+ regulatory T cell

TsCD8+FoxP3+ suppressor T cell.

Electronic supplementary materialThe online version of this article doi:10.1186-2051-1426-2-1 contains supplementary material, which is available to authorized users.

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Author: Andrew Zloza - Dae Won Kim - Seunghee Kim-Schulze - Michael C Jagoda - Vladia Monsurro - Francesco M Marincola - Howard 

Source: https://link.springer.com/







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