Immunogenicity of small‐cell lung cancer associates with STING pathway activation and is enhanced by ATR and TOP1 inhibition

Autor:	Xuetao Li, Yujun Li, Ziwen Zhao, Nabo Miao, Guorong Liu, Liaoyuan Deng, Shuquan Wei, Jun Hou
Jazyk:	angličtina
Rok vydání:	2023
Předmět:	cGAS‐STING pathway DNA damage response immune infiltration small‐cell lung cancer type I IFNs Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Zdroj:	Cancer Medicine, Vol 12, Iss 4, Pp 4864-4881 (2023)
Druh dokumentu:	article
ISSN:	2045-7634
DOI:	10.1002/cam4.5109
Popis:	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. Transcriptomic subsets of SCLC were identified based on STING‐related genes. Distinct mutation and immunogenomic profiles of these subsets were determined. The direct antitumor efficacy and the potential of enhancing antitumor immunity of the strategy using the ATR‐TOP1‐inhibitor combination were tested in SCLC cell lines. Results The intrinsic expression of STING was significantly reduced in SCLC compared to normal lung tissues (p
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