miR-155 Overexpression in OT-1 CD8<sup>+</sup> T Cells Improves Anti-Tumor Activity against Low-Affinity Tumor Antigen.

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Version: Final published version
License: CC BY-NC-ND 4.0
Serval ID
serval:BIB_39DC24C5C585
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
miR-155 Overexpression in OT-1 CD8<sup>+</sup> T Cells Improves Anti-Tumor Activity against Low-Affinity Tumor Antigen.
Journal
Molecular therapy oncolytics
Author(s)
Monnot G.C., Martinez-Usatorre A., Lanitis E., Lopes S.F., Cheng W.C., Ho P.C., Irving M., Coukos G., Donda A., Romero P.
ISSN
2372-7705 (Print)
ISSN-L
2372-7705
Publication state
Published
Issued date
27/03/2020
Peer-reviewed
Oui
Volume
16
Pages
111-123
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Abstract
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 <sup>+</sup> 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.
Keywords
CD8+ T cells, TCR antigen affinity, adoptive cell transfer, microRNA-155, oncoimmunology, therapeutic vaccine
Pubmed
Open Access
Yes
Create date
06/02/2020 17:07
Last modification date
15/01/2021 7:08
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