miR-155 Overexpression in OT-1 CD8+ T Cells Improves Anti-Tumor Activity against Low-Affinity Tumor Antigen

Abstract Therapy by adoptive transfer of ex vivo expanded tumour-infiltrating or genetically modified T cells may lead to impressive clinical responses. However, there is a need to improve in vivo persistence and functionality of the transferred T cells, in particular to face the highly immunosuppressive environment of solid tumours. Here, we investigate the potential of miR-155, a microRNA known to play an important role in CD8+ T cell fitness. We show that forced expression of miR-155 in tumour antigen-specific T cells improves the tumour control of B16 tumours expressing a low affinity antigen ligand. Importantly, miR-155-transduced T cells exhibit increased proliferation and effector functions, associated with a higher glycolytic activity independent of exogenous glucose. Altogether, these data suggest that miR-155 may optimize the antitumor activity of adoptively-transferred low-affinity TILs, in particular by rendering them more resistant to the glucose-deprived environment of solid tumours. Thus, transgenic expression of miR-155 may enable therapeutic targeting of self-antigen specific T cells in addition to neoantigen specific ones.