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6ThiodG induces anti-tumor immunity in SCLC

ABSTRACT: 6ThiodG induces anti-tumor immunity in SCLC

PROVIDER: PRJNA933593 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR23399526.fastq.gz	Fastqsanger.gz
	SRR23399527.fastq.gz	Fastqsanger.gz

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6ThiodG induces anti-tumor immunity in SCLC

Project description:There are few effective treatments for small cell lung cancer (SCLC). We explored a major dependency of small cell lung cancer as a therapeutic target. Nearly all of SCLCs have telomerase activity and they are dependent on this enzyme for their ability to continuously divide. We utilized a nucleoside analog, 6-Thio-2’-deoxyguanosine (6TdG), that is preferentially recognized by telomerase to promote telomere dysfunction. Low and intermittent doses of 6TdG inhibited tumor growth and metastasis from the primary tumors. Anti-tumor activity of 6TdG was associated with decrease in cancer initiation cell (CIC) markers L1CAM/CD133 and increase in visibility to innate and adaptive immunity. Mechanistically, 6TdG depleted CICs and induced type-I interferon signaling by activating tumor STING. We confirmed the functional essential role of CIC markers L1CAM/CD133 in SCLC tumor initiation. We also observed dramatic synergy between 6TdG and irradiation in both syngeneic and humanized SCLC models that was dependent on immune cells.

2023-12-11 | GSE225018 | GEO

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