A dormant TIL phenotype defines non-small cell lung carcinomas sensitive to immune checkpoint blockers

doi:10.1038/s41467-018-08195-6

GSTDTAP > 资源环境科学

DOI	10.1038/s41467-018-08195-6
	A dormant TIL phenotype defines non-small cell lung carcinomas sensitive to immune checkpoint blockers
	Gettinger, S. N.1; Choi, J.2; Mani, N.3,4; Sanmamed, M. F.5; Datar, I.3,4; Sowell, Ryan 5; Du, Victor Y.5; Kaftan, E.1,4; Goldberg, S.1; Dong, W.2; Zelterman, D.6; Politi, K.1,3; Kavathas, P.5,7; Kaech, S.5; Yu, X.6; Zhao, H.2,6; Schlessinger, J.8; Lifton, R.2; Rimm, D. L.1,3; Chen, L.5; Herbst, R. S.1; Schalper, K. A.1,3,4
	2019-01-18
发表期刊	NATURE COMMUNICATIONS
ISSN	2041-1723
出版年	2018
卷号	9
文章类型	Article
语种	英语
国家	USA
英文摘要	The biological determinants of sensitivity and resistance to immune checkpoint blockers are not completely understood. To elucidate the role of intratumoral T-cells and their association with the tumor genomic landscape, we perform paired whole exome DNA sequencing and multiplexed quantitative immunofluorescence (QIF) in pre-treatment samples from non-small cell lung carcinoma (NSCLC) patients treated with PD-1 axis blockers. QIF is used to simultaneously measure the level of CD3+ tumor infiltrating lymphocytes (TILs), in situ T-cell proliferation (Ki-67 in CD3) and effector capacity (Granzyme-B in CD3). Elevated mutational load, candidate class-I neoantigens or intratumoral CD3 signal are significantly associated with favorable response to therapy. Additionally, a "dormant" TIL signature is associated with survival benefit in patients treated with immune checkpoint blockers characterized by elevated TILs with low activation and proliferation. We further demonstrate that dormant TILs can be reinvigorated upon PD-1 blockade in a patient-derived xenograft model.
领域	资源环境
收录类别	SCI-E
WOS记录号	WOS:000441306000003
WOS关键词	T-CELLS ; PD-1 BLOCKADE ; MUTATIONAL LANDSCAPE ; CTLA-4 BLOCKADE ; NIVOLUMAB ; CANCER ; NEOANTIGENS ; IPILIMUMAB ; IDENTIFICATION ; LYMPHOCYTES
WOS类目	Multidisciplinary Sciences
WOS研究方向	Science & Technology - Other Topics
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引用统计
文献类型	期刊论文
条目标识符	http://119.78.100.173/C666/handle/2XK7JSWQ/204176
专题	资源环境科学
作者单位	1.Yale Canc Ctr, New Haven, CT 06511 USA; 2.Yale Sch Med, Dept Genet, New Haven, CT 06511 USA; 3.Yale Sch Med, Dept Pathol, New Haven, CT 06511 USA; 4.Yale Canc Ctr, Translat Immunooncol Lab, New Haven, CT 06511 USA; 5.Yale Sch Med, Immunobiol, New Haven, CT 06511 USA; 6.Yale Sch Publ Hlth, New Haven, CT 06511 USA; 7.Yale Sch Med, Lab Med, New Haven, CT 06511 USA; 8.Yale Sch Med, Dept Pharmacol, New Haven, CT 06511 USA
推荐引用方式 GB/T 7714	Gettinger, S. N.,Choi, J.,Mani, N.,et al. A dormant TIL phenotype defines non-small cell lung carcinomas sensitive to immune checkpoint blockers[J]. NATURE COMMUNICATIONS,2019,9.
APA	Gettinger, S. N..,Choi, J..,Mani, N..,Sanmamed, M. F..,Datar, I..,...&Schalper, K. A..(2019).A dormant TIL phenotype defines non-small cell lung carcinomas sensitive to immune checkpoint blockers.NATURE COMMUNICATIONS,9.
MLA	Gettinger, S. N.,et al."A dormant TIL phenotype defines non-small cell lung carcinomas sensitive to immune checkpoint blockers".NATURE COMMUNICATIONS 9(2019).