Ablation-induced activation of the cGAS–STING pathway: A promising strategy to enhance immune checkpoint therapy in non-small-cell lung cancer

Lung cancer is the leading cause of cancer-related morbidity and mortality in China, and it poses significant treatment challenges. Ablation therapy has gained prominence for local control of early-stage and oligometastatic disease. The cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS–STING) pathway plays a central role in the activation of innate immune and durable anti-tumor responses by reshaping the tumor microenvironment. Emerging evidence suggests that ablation not only directly destroys tumor tissue, but it also activates immune pathways, including cGAS–STING, thereby enhancing anti-tumor immunity. These insights have fueled interest in combining ablation with STING agonists to potentiate immune checkpoint therapies. In this review, current understanding of the immunomodulatory effects of ablation is summarized, and the synergistic potential of integrating cGAS–STING-targeted strategies into lung cancer immunotherapy.