Gene expression profile of CD8 T cells from the responder and non-responder mice following immunotherapy treatment for prostate cancer

Immunotherapy represents a novel treatment approach for cancer; however, a longer maturation time and the lack of immunological markers are major obstacles in the development and characterization of immunological therapies. This study aims to identify gene expression profile on CD8+ T cells between the responder (completely regressed tumors) and non-responder (progressively growing tumors) groups of mice helpful in predicting the outcome of immunotherapy treatment. Using a preclinical mouse model for prostate cancer, subcutaneous tumors were established and the mice were treated with Ad-PSA+PSCA bivalent vaccine. Splenic CD8+ T cells purified from the responder and non-responder groups of mice were subjected to Affymetrix microarray to obtain gene expression profile. Pooling the data sets from two independent experiments revealed an up-regulation of 85 genes (>2.0 fold; p =2.7e-63) and down-regulation of 1768 gene (>2.0 fold; p =1.0e-63) in CD8+ T cells from the non-responder mice. Gene network analysis showed a coordinated expression of genes implicated in cellmediated immune response, cell-to-cell signaling and interaction, and immune cell trafficking. The mRNA expression levels for the selected transcripts were verified using semi-quantitative RT-PCR method suggesting a panel of genes specific to CD8+ T cells differentially expressed between the responder and non-responder mice. Further studies are warranted to determine the potential of these identified genes as immunological biomarker to predict immunotherapy response. Authors’ details Urology, The University of Kansas Medical Center, Kansas City, KS, USA. Molecular and Integrative Physiology, The University of Kansas Medical Center, Kansas City, KS, USA. Internal Medicine, The University of Kansas Medical Center, Kansas City, KS, USA.