Identification of miRNAs involved in T cell programming for future use in the design and monitoring of adoptive cellular transfer

Abstract

The recent discovery of miRNAs, small single-stranded non-coding RNAs that can specifically repress protein expression, has revealed a critical new layer of gene expression regulation that affects many biological systems, including the mammalian immune system. Using miRNA microarrays, we are examining the role of miRNAs in the process of CD8+ T cell differentiation. Understanding the role miRNAs play in T cell differentiation could enhance our ability to culture in vitro optimum T cells for in vivo tumour killing by adoptive cell transfer (ACT) cancer therapies, whereby a patient’s own cancer-specific T cells are cultured ex-vivo and reinfused. Studies have shown that the efficacy of this type of therapy is related to the differentiation status of the T cells, but current culturing protocols, using IL2, do not yield optimally differentiated T cells. In our laboratory we are developing new culture methods, using IL7, to generate T cells that, based on markers of differentiation, should be more effective when used in ACT therapies. Once we have identified miRNAs critical to the differentiation process it may be possible to manipulate their expression, and therefore a T cell’s differentiation status.