Vascular STING activation facilitates NK cell anti-tumor immunity in small cell lung cancer - PubMed
3 days ago
- #NK cells
- #STING signaling
- #small cell lung cancer
- Small cell lung cancer (SCLC) typically has a 'cold' tumor microenvironment with limited immune infiltration.
- Neuroendocrine SCLC cells repress MHC-I expression, making them susceptible to NK cell-mediated cytotoxicity.
- Effector immune cells, including NK cells, are excluded from MHC-Ilow/neg SCLC regions in patient samples.
- Dynamic single-cell RNA sequencing (DynaMITE-seq) and spatial transcriptomics reveal the microvasculature as a major checkpoint restricting NK cell extravasation/recruitment.
- Activation of vascular STING signaling restores NK cell infiltration and killing of neuroendocrine SCLC.
- This suggests a strategy to overcome SCLC immunologic barriers and enhance therapeutic response to DLL3-targeted CAR-NK cell therapy.