STING signaling in T cells: Relevance in cancer immunotherapy

The achievements in cancer immunotherapy thanks to the use of immune check-point inhibitors show that harnessing the anticancer activity of immune cells can translate into clinical successes. While these observations urge immunologists to pursue investigations, many patients still do not respond to treatments with immune checkpoint inhibitors, underscoring the need to identify alternate immunotherapy strategies. The STING (Stimulator of Interferon Genes) protein, initially characterized by the group of Glen Barber as a key molecule responsible for antiviral defense, has become an interesting therapeutic target in oncology and its rele-vance is currently being tested in clinical trials. STING is expressed in different sub-populations of immune cells. While STING activation in dendritic cells triggers effector immune responses, the outcome of STING activation in T cells remains elusive. Although initial studies suggested that engaging STING signaling in T cells triggered cell death, subsequent investigations instead proposed that STING could promote effector T cell functions. Our recent studies also unra-vel that cell-intrinsic STING signaling in CD4 T cells shapes CD4 T cell differentiation. In this review, we discuss the molecular mechanisms associated with STING activation in T cells and the potential implications for the design of cancer immunotherapy strategies.(c) 2022 l'Academie nationale de medecine. Published by Elsevier Masson SAS. All rights reserved.

Automated summary

The use of immune check-point inhibitors in cancer immunotherapy has led to significant achievements, demonstrating the potential of immune cells in fighting cancer. However, many patients do not respond to this treatment, highlighting the need for alternative immunotherapy strategies. The STING protein, known for its role in antiviral defense, has emerged as a promising therapeutic target in oncology and is currently being investigated in clinical trials. While the activation of STING in dendritic cells triggers immune responses, its impact on T cell function remains unclear. This review explores the molecular mechanisms of STING activation in T cells and its implications for the development of cancer immunotherapy strategies.