Vascular STING activation facilitates NK cell anti-tumor immunity in small cell lung cancer.
Small cell lung cancer (SCLC) typically displays a "cold" tumor microenvironment with a paucity of immune infiltrate.
APA
Campisi M, Osaki T, et al. (2026). Vascular STING activation facilitates NK cell anti-tumor immunity in small cell lung cancer.. Cancer cell, 44(4), 858-878.e16. https://doi.org/10.1016/j.ccell.2026.02.008
MLA
Campisi M, et al.. "Vascular STING activation facilitates NK cell anti-tumor immunity in small cell lung cancer.." Cancer cell, vol. 44, no. 4, 2026, pp. 858-878.e16.
PMID
41791380
Abstract
Small cell lung cancer (SCLC) typically displays a "cold" tumor microenvironment with a paucity of immune infiltrate. Neuroendocrine SCLC cells also profoundly repress MHC-I expression, rendering them vulnerable to NK cell-mediated cytotoxicity. Here, we confirm that neuroendocrine SCLC cells are sensitive to NK cell-mediated attack, yet the quantitative spatial profiling of the SCLC immune microenvironment in patient samples reveals that effector immune cells, including NK cells, are excluded from MHC-I SCLC regions. To study this biology, we develop dynamic single-cell RNA sequencing of microphysiological immune tumor environments (DynaMITE-seq) and integrate findings with spatial transcriptomics in patient tissue, unveiling the microvasculature as a major checkpoint restricting NK cell extravasation/recruitment. We demonstrate that the activation of vascular Stimulator of Interferon Genes (STING) signaling restores NK cell infiltration and killing of neuroendocrine SCLC, suggesting a strategy to overcome this key SCLC immunologic barrier and prime therapeutic response to DLL3-targeted CAR-NK cell therapy.
MeSH Terms
Humans; Killer Cells, Natural; Small Cell Lung Carcinoma; Lung Neoplasms; Membrane Proteins; Tumor Microenvironment; Animals; Mice; Cell Line, Tumor; Signal Transduction; STING Protein