STING predicts patterns of failure in locally advanced head and neck squamous cell carcinoma.

The TMEM173/STING protein is linked to therapeutic resistance in preclinical models of HNSCC (Head and neck squamous cell carcinoma). To evaluate STING as a biomarker, quantitative immunofluorescence (QIF) was performed on a tissue microarray (TMA) cohort of primary HNSCC (n = 72). Cytokeratin and 4,6-diamidino-2-phenylindole (DAPI) staining were used to differentiate between tumor or stromal compartments, and patient groups were dichotomized based on STING QIF scores. HNSCCs display variable STING protein levels in both tumor cell and stromal compartments. STING QIF score in tumor cells is associated with p16 positivity, with similar nonsignificant trends observed for stromal QIF values. In cohort 1, elevated STING levels in either tumor cells (P = .029) or stroma (P = .023) significantly improved DFS. These findings were validated in a second oropharyngeal HNSCC TMA cohort (n = 92) where borderline or significant differences in DFS were observed for elevated STING in tumor cells (P = .066) or the stroma (P = .028). A more detailed breakdown of failure patterns in cohort 2 revealed that elevated STING in tumor (P = .015) or stroma (P = .054) predicts local-regional control, and a trend for reduced distant failure was also observed for elevated stromal STING (P = .067). Local-regional recurrence was rare in HPV+ tumors and occurred only with low STING expression. In multivariate analysis, p16 was a significant predictor for local control, whereas elevated STING was of borderline significance (P = .051). These results suggest that STING protein levels in the tumor cell are a biomarker for predicting HNSCC local control after radiation therapy, and elevated STING in tumor stroma may be associated with a reduced risk of distant failure.