2022
DOI: 10.1002/cam4.5109
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Immunogenicity of small‐cell lung cancer associates with STING pathway activation and is enhanced by ATR and TOP1 inhibition

Abstract: Introduction The activation of STING (stimulator of interferon genes) pathway enhances antitumor immunity in small‐cell lung cancer (SCLC), while the DNA damage induced by non‐cGAMP‐based agonists is a potent inducer of STING activity. Here, we investigate the intrinsic expression of STING in cancer cells and evaluate the value of the combination of ATR and TOP1 inhibitors in enhancing antitumor immunity. Methods STING expression was assessed at mRNA and protein levels in SCLC and normal lung tissues. Transcri… Show more

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Cited by 17 publications
(7 citation statements)
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“…A recent investigation pointed to another option to assess the possibility of immunotherapy: high expression of stimulator of interferon genes (STING) was associated with enrichment with immune cell infiltration. As STING expression can be therapeutically influenced, this opens another treatment option ( 63 ).…”
Section: Discussionmentioning
confidence: 99%
“…A recent investigation pointed to another option to assess the possibility of immunotherapy: high expression of stimulator of interferon genes (STING) was associated with enrichment with immune cell infiltration. As STING expression can be therapeutically influenced, this opens another treatment option ( 63 ).…”
Section: Discussionmentioning
confidence: 99%
“…It was found that the STING-low subtype was enriched with pathways related to DNA damage response and cell cycle progression in SCLC. The relationship between DDR pathway activity and STING-IFN innate immune response was confirmed again by in vitro experiments using ATR inhibitors and TOP1 inhibitors [ 42 ]. These results suggest that the combination of DDRI and ICIs, through activating the cGAS-STING pathway, could have a certain clinical value in overcoming the primary and secondary resistance of small cell lung cancer to ICI.…”
Section: Application Of Cgas-sting Pathway In Lung Cancermentioning
confidence: 94%
“…An interesting observation suggested that the use of the chemo-immunotherapeutic approach, combining the topo-active drug teniposide with anti-PD1 antibodies, shows promise for enhanced antitumor efficacy in mouse tumor models, with implications for the STING pathway [214,215]. Recent emphasis on antibody-drug conjugates, like trastuzumab-L6 and the DNA TOPI inhibitor MF-6, highlights their role in achieving immunogenic tumor cell death [216,217].…”
Section: Immune Checkpoint Inhibitors and Topo-active Drugsmentioning
confidence: 99%