Effect of oncolytic virotherapy on immune microenvironment in immune subtypes identified in gastric cancer and hepatocellular carcinoma

Abstract

Tumor occurrence and progression are significantly influenced by immunity, and the immune infiltration and immune-related gene expression in solid tumors are closely correlated to the response of patients to immunotherapy. In this study, the level of tumor infiltrating immune cells in gastric cancer and hepatocellular carcinoma samples from the TCGA database were assessed using ssGSEA, and the tumor samples were divided into two subtypes (Imm_H and Imm_L) with different immune cell infiltration level. The differences in immune cell percentage and immune checkpoint gene expression between the two subtypes indicated that the Imm_H group had higher levels of immune infiltration, but also more infiltrated immunosuppressive cells and higher mRNA levels of immune checkpoint genes. Then the immune subtype-specific gene network was built and the main modules representing the genes and functions that differ between the two immune subtypes were identified. To explore the effect of oncolytic virus on tumor immune microenvironment, we constructed the previously developed synthetic adenovirus containing the synthetic sensory switch gene circuit, assessed the antitumor effect in mouse models, and measured the proportion of different cell types by single-cell RNA sequencing. The results showed that synthetic oncolytic virus inhibited tumor development and altered the proportion of infiltrating immune cells, suggesting that synthetic oncolytic virus may have different mechanism on the two immune subtypes. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=168 HEIGHT=200 SRC="FIGDIR/small/524374v1_ufig1.gif" ALT="Figure 1"> View larger version (42K): org.highwire.dtl.DTLVardef@dffa9dorg.highwire.dtl.DTLVardef@be8e2eorg.highwire.dtl.DTLVardef@68acf6org.highwire.dtl.DTLVardef@33862f_HPS_FORMAT_FIGEXP M_FIG C_FIG