STING suppresses the reactivation of dormant metastasis

Metastatic relapse frequently develops from disseminated cancer cells that remain
dormant in distant organs after the apparently successful treatment of a primary tumor.
Disseminated cancer cells fluctuate between immune evasive quiescent and cell cycle reentry
states, which exposes them to elimination by the immune system1-5. Little is known about the
molecules that determine immune-mediated clearing of awakened metastatic cells and how this
process could be therapeutically activated to eliminate residual disseminated disease in patients.
Here, we use models of indolent metastasis to identify cancer cell-intrinsic determinants of
immune reactivity during cancer cell exit from dormancy. Through in vivo genetic screens of
tumor-intrinsic immune regulators, we identified the STING (stimulator of interferon genes)
pathway as a major suppressor of metastatic outbreak in dormant models of human and mouse
lung adenocarcinoma metastasis. STING levels and signaling activity rise in metastatic
progenitors that enter the cell cycle and are dampened by epigenetic silencing in overt
metastases. Induction of STING signaling in aggressive cancer cells derived from metastatic
outbreaks suppresses metastasis in a NK cell and T cell-dependent manner. Systemic treatment
of mice with pharmacologic STING agonists eliminates indolent metastatic cells and prevents
spontaneous metastasis. Thus, STING signaling represents a checkpoint against the progression
of dormant metastasis and suggests a therapeutically actionable strategy for the prevention of
disease relapse.

Here we provided files and codes for the CRISPR screen and single-cell RNA-seq data analysis. 

PATIENT_LUNG_ADENOCARCINOMA_ANNOTATED.h5 and MOUSE_LUNG_ADENOCARCINOMA_METASTASIS_ANNOTATED.h5 can be downloaded from dpeerlab/lung-development-cancer-progression: Single cell analysis in regenerative lineages and immune-mediated pruning in lung cancer metastasis (github.com)