4.6 Article

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

期刊

IMMUNOLOGY
卷 167, 期 4, 页码 495-507

出版社

WILEY
DOI: 10.1111/imm.13549

关键词

immunotherapy; lung cancer; nontumor expression; predictive biomarker; TMEM173

资金

  1. Jiangsu Provincial Social Development General Program [BE20197180]
  2. Jiangsu Provincial Social Development - Key Projects - Clinical Frontier Technologies [BE2019719]
  3. National Natural Science Foundation of China [81772500]

向作者/读者索取更多资源

The stimulator of interferon genes (STING) pathway plays a crucial role in anticancer immune responses, particularly in non-small cell lung cancer (NSCLC). This study demonstrates that STING in host cells, not tumor cells, mediates the therapeutic efficacy of anti-PD-1 inhibitors in NSCLC patients. These findings suggest that STING could be used as a marker to select NSCLC patients who may benefit from immunotherapy.
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.

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