Host stimulator of interferon genes is essential for the efficacy of anti-programmed cell death protein 1 inhibitors in non-small cell lung cancer

Abstract

The stimulator of interferon genes (STING) pathway is important for anticancer immune responses. However, the relative contributions of host and tumour STING in anti-programmed cell death protein 1 (anti-PD-1) inhibitor responses in non-small cell lung cancer (NSCLC) are unknown. STING expression in tumour and blood was associated with anti-PD-1 therapy in NSCLC patients; Moreover, loss of PD-1 inhibitor therapeutic potency was demonstrated in STING KO (knock out) splenocytes and STING KO mice. STING knock-down in tumour cells had no effect. STING on CD8⁺ T cells and host cells, not tumour cells, correlated with clinical effect of anti-PD-1 therapy in NSCLC patients. Finally, adoptive transfer of CD8⁺ T cells restored PD-1 inhibitor anticancer effects. STING in host cells but not in tumour cells mediates anti-PD-1 inhibitor responses in cancer immunotherapy and could be used to select advantageous NSCLC patients from immunotherapy.

Keywords: TMEM173; immunotherapy; lung cancer; nontumor expression; predictive biomarker.