High cGAS-STING expression associates with improved efficacy of neoadjuvant chemo-immunotherapy in head and neck squamous cell carcinoma

作者：Miao Wang, Menglin Shi, Yiming Ding, Zishanbai Zhang, Yuze Ge, Zhixin Li, Yixin Jing, Hu HongLian, Xiaohong Chen · 发表于：Frontiers in Oncology · 年份：2025 · DOI：10.3389/fonc.2025.1584061 · 被引用次数：1 · 研究领域：interferon and immune responses、Immune Cell Function and Interaction、Cancer-related molecular mechanisms research

Purpose Neoadjuvant chemo-immunotherapy (NACI) has demonstrated significant clinical advantages in head and neck squamous cell carcinomas (HNSCC), while clinical responses vary in different patients. This study investigated the correlation between the cyclic GMP-AMP synthase (cGAS, CGAS ) and the stimulator of interferon genes (STING, STING1 ) expressions and the efficacy of NACI in HNSCC. Methods The correlation between CGAS and STING1 expressions and chemotherapy/immunotherapy drug sensitivity was analyzed using the GDSC and TCIA dataset. The study enrolled 38 HNSCC patients receiving NACI, with protein expressions of cGAS and STING evaluated via immunohistochemistry. The T cell abundance and tumor-T cell interactions in different CGAS and STING1 expression groups were analyzed using bulk RNA-seq and scRNA-seq data from open databases. Results The mRNA expressions of CGAS and STING1 were negatively correlated with the IC50 of docetaxel and positively correlated with the efficacy of anti-PD-1 treatment (p<0.05). In the real-world cohort, cGAS and STING expressions were both positively related to NACI efficacy (p<0.05). The mRNA expressions of CGAS and STING1 were positively correlated with the abundance of Act-CD4 ( CGAS : rho=0.416, p<2.21e-16; STING1 : rho=0.26, p=1.82e-09), Act-CD8 ( CGAS : rho=0.089, p=0.0425; STING1 : rho=0.303, p=1.98e-12), NKT cell ( CGAS : rho=0.255, p=0.3.78e-09; STING1 : rho=0.375, p=2.2e-6). Tumor cells with increased expressi...