[HTML][HTML] miR-155 overexpression in OT-1 CD8+ T cells improves anti-tumor activity against low-affinity tumor antigen

GC Monnot, A Martinez-Usatorre, E Lanitis… - Molecular Therapy …, 2020 - cell.com
GC Monnot, A Martinez-Usatorre, E Lanitis, SF Lopes, WC Cheng, PC Ho, M Irving
Molecular Therapy-Oncolytics, 2020cell.com
Therapy by adoptive transfer of ex vivo-expanded tumor-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 tumors. 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 tumor antigen-specific T cells improves the tumor control of B16 …
Therapy by adoptive transfer of ex vivo-expanded tumor-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 tumors. 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 tumor antigen-specific T cells improves the tumor control of B16 tumors 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 tumor-infiltrating lymphocytes (TILs), in particular, by rendering them more resistant to the glucose-deprived environment of solid tumors. Thus, transgenic expression of miR-155 may enable therapeutic targeting of self-antigen-specific T cells in addition to neoantigen-specific ones.
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