@article {1656921,
	title = {MPS1 inhibition primes immunogenicity of KRAS-LKB1 mutant lung cancer},
	journal = {Cancer Cell},
	volume = {40},
	number = {10},
	year = {2022},
	month = {2022 Oct 10},
	pages = {1128-1144.e8},
	abstract = {KRAS-LKB1 (KL) mutant lung cancers silence STING owing to intrinsic mitochondrial dysfunction, resulting in T\&nbsp;cell exclusion and resistance to programmed cell death (ligand) 1 (PD-[L]1) blockade. Here we discover that KL cells also minimize intracellular accumulation of 2{\textquoteright}3{\textquoteright}-cyclic GMP-AMP (2{\textquoteright}3{\textquoteright}-cGAMP) to further avoid downstream STING and STAT1 activation. An unbiased screen to co-opt this vulnerability reveals that transient MPS1 inhibition (MPS1i) potently re-engages this pathway in KL cells via micronuclei generation. This effect is markedly amplified by epigenetic de-repression of STING and only requires pulse MPS1i treatment, creating a therapeutic window compared with non-dividing cells. A single course of decitabine treatment followed by pulse MPS1i therapy restores T\&nbsp;cell infiltration in\&nbsp;vivo, enhances anti-PD-1 efficacy, and results in a durable response without evidence of significant toxicity.},
	keywords = {Decitabine, Genes, ras, Humans, Ligands, Lung Neoplasms, Proto-Oncogene Proteins p21(ras)},
	issn = {1878-3686},
	doi = {10.1016/j.ccell.2022.08.015},
	author = {Kitajima, Shunsuke and Tani, Tetsuo and Springer, Benjamin F and Campisi, Marco and Osaki, Tatsuya and Haratani, Koji and Chen, Minyue and Knelson, Erik H and Mahadevan, Navin R and Ritter, Jessica and Yoshida, Ryohei and K{\"o}hler, Jens and Ogino, Atsuko and Nozawa, Ryu-Suke and Sundararaman, Shriram K and Thai, Tran C and Homme, Mizuki and Piel, Brandon and Kivlehan, Sophie and Obua, Bonje N and Purcell, Connor and Yajima, Mamiko and Barbie, Thanh U and Lizotte, Patrick H and J{\"a}nne, Pasi A and Paweletz, Cloud P and Gokhale, Prafulla C and Barbie, David A}
}
