Transcriptome Signature of Immune Cells Post Reovirus Treatment in Mutated Colorectal Cancer.

Purpose: Reovirus propagates with high efficiency in mutated colorectal cancer (CRC). About 45-50% of CRC patients possess a mutation. Oncolytic reovirus treatment in combination with chemotherapy was tested in patients possessing mutated metastatic CRC. This study evaluates the biological responses to reovirus treatment by determining the gene expression patterns in RAS-related signaling pathways.

Methods: Reovirus was administered as a 60-min intravenous infusion for 5 consecutive days every 28 days, at a tissue culture infective dose (TCID) of 3×10. Peripheral blood mononuclear cells (PBMCs) were isolated from whole-blood pre- and post-reovirus administration at 48 hr, day-8, and day-15. Clariom_D_Human_Assay was used to determine the expression of vital genes compared to pre-reovirus treatment by RNA sequencing. Using exported sample signals, ΔΔCt method was used to analyze the fold changes of genes within seven gene pathways. Significance was calculated by students-two-tail-test. Hierarchical clustering dendrogram was constructed by calculating Pearson's correlation coefficients.

Results: As compared to the control, [48 hr; 2.49X], [48 hr; 2.24X], [D8, D15; 2.27X, 3.16X], [D15; 1.70X], [48 hr, D15; 1.89X, 4.54X], [48 hr; 4.66X], [48 hr; 4.54X], [D8, D15; 19.0X, 1.42X], [D8, D15; 2.11X, 1.77X], and [D8; 1.45X] are upregulated post-reovirus. [D15; 0.61X], [D8, D15; 0.78X, 0.71X], [D8; 0.62X], [48 hr, D8, D15; 0.44X, 0.28X, 0.28X], [D15; 0.69X], and [D8; 0.73X] are downregulated post-reovirus. Fold change values were significant [p<0.05].

Conclusion: This study highlights reovirus as a novel treatment option for mutated CRC and showcases its effect on the expression of crucial genes.