Skip to Main content Skip to Navigation
Preprints, Working Papers, ...

Low STING expression in a transplantable KrasG12D/P53ko lung cancer model contributes to SiglecF+ neutrophil and CD103+Treg accumulation in tumors

Abstract : Lung cancer is the leading cause of mortality by cancer worldwide. Non-small cell lung cancer is the most common type of lung cancer and mutations in the KRAS gene are frequently found in this pathology. While immune checkpoint inhibitors are providing new hope for lung cancer care, only a subset of patients show durable benefit from these new therapies designed to drive an efficient anti-tumor immune response. Hence, it is crucial to better understand the mechanisms through which the tumor immune microenvironment is established in lung tumors. Using bioinformatics, we observed that high expression of the STimulator of INterferon Gene (STING) associates with a longer overall survival specifically in KRAS mutant cancer patients. In lung cancer cell lines, STING expression is linked to interferon response and epithelial-to-mesenchymal transition. Because STING activation in immune cells of the tumor microenvironment using specific agonists is an emerging strategy to trigger an anti-tumor immune response, we took advantage of two transplantable models of Kras driven lung cancer, expressing high or low levels of STING, to investigate the function of STING directly in cancer cells in vivo. We observed that high-STING expression and constitutive STING signaling were critical for transplanted tumor formation rather than playing a major role in tumor immunogenicity. Besides, low-STING expression in cancer cells is associated with an immunosuppressive tumor microenvironment characterized by the accumulation of tumor promoting SiglecF+ neutrophils and CD103+ regulatory T cells. In that model, knocking out STING increased the early response to anti-PD1 treatment. We conclude that low-STING expression in cancer cells might confer them an independence from pro-inflammatory signals and a greater immunosuppressive capability and aggressiveness.
Document type :
Preprints, Working Papers, ...
Complete list of metadata

https://hal.archives-ouvertes.fr/hal-03368347
Contributor : Laurent Gros Connect in order to contact the contributor
Submitted on : Wednesday, October 6, 2021 - 4:48:12 PM
Last modification on : Friday, October 22, 2021 - 2:56:13 PM

File

2021.01.04.425311v2.full(1).pd...
Files produced by the author(s)

Identifiers

Citation

Laurent Gros, Chiara Ursino, Julie Constanzo, Nadine Zangger, Etienne Meylan, et al.. Low STING expression in a transplantable KrasG12D/P53ko lung cancer model contributes to SiglecF+ neutrophil and CD103+Treg accumulation in tumors. 2021. ⟨hal-03368347⟩

Share

Metrics

Record views

19

Files downloads

30