cGAS-STING pathway reprograms macrophage polarization and is highly expressed in responding tumors after neoadjuvant immunotherapy in head and neck carcinoma

• Elevated STING (TMEM173) expression correlates with increased M1 macrophage infiltration and activation of polarization-related pathways in HNSCC. • The STING agonist MSA-2 reprograms M2 macrophages toward an M1 phenotype, upregulating pro-inflammatory cytokines and enhancing antigen presentation markers. • High STING expression in clinical samples is associated with increased M1-like macrophage infiltration, supporting its role in antitumor immunity. • Single-cell RNA-seq data from HNSCC patients on neoadjuvant immunotherapy reveal higher cGAS-STING pathway activity in responders, suggesting STING agonists as a promising combination strategy.