Big Data Offers Novel Insights for Oncolytic Virus Immunotherapy

Abstract

Large-scale assays, such as microarrays, next-generation sequencing and various "omics" technologies, have explored multiple aspects of the immune response following virus infection, often from a public health perspective. Yet a lack of similar data exists for monitoring immune engagement during oncolytic virus immunotherapy (OVIT) in the cancer setting. Tracking immune signatures at the tumour site can create a snapshot or longitudinally analyse immune cell activation, infiltration and functionality within global populations or individual cells. Mapping immune changes over the course of oncolytic biotherapy-from initial infection to tumour stabilisation/regression through to long-term cure or escape/relapse-has the potential to generate important therapeutic insights around virus-host interactions. Further, correlating such immune signatures with specific tumour outcomes has significant value for guiding the development of novel oncolytic virus immunotherapy strategies. Here, we provide insights for OVIT from large-scale analyses of immune populations in the infection, vaccination and immunotherapy setting. We analyse several approaches to manipulating immune engagement during OVIT. We further explore immunocentric changes in the tumour tissue following immunotherapy, and compile several immune signatures of therapeutic success. Ultimately, we highlight clinically relevant large-scale approaches with the potential to strengthen future oncolytic strategies to optimally engage the immune system.

Keywords: immune; immunology; immunotherapy; large-scale; oncolytic; screen; virus.

Figure 1

Analysing immune targets using large-scale technologies in the tumour setting following infection/therapy. (A) The immune response to infection or immunotherapy in the tumour setting can be captured at multiple different timepoints, including prior to infection/therapy (left), during infection/therapy as cancer cells begin to die (middle), and following infection/therapy when the tumour has been ablated or reduced in bulkiness (right); (B) Large-scale immune analysis can be performed at the level of a single immune cell, an immune cell population or multiple immune cell populations; (C) Several key large-scale techniques can capture genomic, transcriptomic, proteomic or metabolomic changes at the immune level. When assays have been appropriately replicated and validated, matched data generated at the DNA, RNA and protein level can subsequently be integrated to achieve a systems biology approach. Abbreviations: CE = Capillary Electrophoresis, GC = Gas Chromatography, HPLC = High Performance Liquid Chromatography, MS = Mass Spectrometry, NGS = Next-Generation Sequencing, NMR = Nuclear Magnetic Resonance, RNASeq = RNA Sequencing, SILAC = stable isotope labelling by amino acids in cell culture, WGS = Whole Genome Sequencing.