STING-driven activation of T cells: relevance for the adoptive cell therapy of cancer
Authors:Fabian Richter1,2, Christophe Paget1,2 and Lionel Apetoh3
1 Centre d’Étude des Pathologies Respiratoires, U1100, INSERM, Tours, France.
2 Faculté de Médecine, Université de Tours, Tours, France.
3 Brown Center for Immunotherapy, Indiana University Melvin and Bren Simon Comprehensive Cancer Center, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Keywords:
Adoptive T cell therapy, STING, T cells, cancer, immunomodulation.
Abbreviatons:
ACT – adoptive cell therapy,
TME – tumor microenvironment,
STING – stimulator of interferon genes,
DC – dendritic cell,
ICI – immune checkpoint inhibitors,
TILs – tumor-infiltrating lymphocytes,
TCR – T cell receptor,
CAR-T – chimeric antigen receptor T cells,
MHC – major histocompatibility complex,
TLRs – Toll-like receptors,
NOD – nucleotide-binding oligomerization domain,
NLRs – NOD-like receptors,
RIG-I – Retinoic acid-inducible gene I,
RLRs – RIG-I-like receptors,
CLRs – C-type lectin receptors,
cGAS – cGAMP synthase,
IRF3 – interferon regulatory factor 3,
IFNs – type I interferons,
APCs – antigen-presenting cells.
Corresponding Author(s):
Conflict of interest statement:
L.A. is a consultant for Brenus-Pharma. L.A. performed consultancy work for Roche, Merck, Bristol-Myers Squibb, and Orega Biotech and was a recipient of a research grant from Sanofi.
Please cite this article as:
Fabian Richter, Christophe Paget and Lionel Apetoh (2023). STING-driven activation of T cells: relevance for the adoptive cell therapy of cancer. Cell Stress 7(11): 95-104. doi: 10.15698/cst2023.11.291
© 2023 Richter et al. This is an open-access article released under the terms of the Creative Commons Attribution (CC BY) license, which allows the unrestricted use, distribution, and reproduction in any medium, provided the original author and source are acknowledged.
Abstract:
Adoptive cell therapy (ACT) can successfully treat hematopoietic cancers but lacks efficacy against solid tumors. This is due to insufficient T cell infiltration, high tumor heterogeneity, frequent antigen loss with subsequent tumor escape, and the immunosuppressive tumor microenvironment (TME). Alternative methods to boost the anticancer efficacy of adoptively transferred cells are actively pursued. Among adjuvants that are utilized to stimulate anticancer immune responses, ligands of the stimulator of interferon genes (STING) pathway have received increasing attention. STING activation can trigger dendritic cell (DC) activation and endogenous immune responses, thereby preventing tumor escape. Activation of the STING pathway in the context of ACT was accordingly associated with improved T cell trafficking and persistence in the TME combined with the reduced presence of immunosuppressive cells. Recent findings also suggest cell-intrinsic effects of STING ligands on T cells. Activation of the STING signaling pathway was in this regard shown to enhance effector functions of CD4+ and CD8+ T cells, suggesting that the STING signaling could be exploited to harness T cell anticancer functions. In this review, we will discuss how the STING signaling can be used to enhance the anticancer efficacy of ACT.