Molecular and Genetic Properties of Tumors Associated with Local Immune Cytolytic Activity

被引：2802

作者：

Rooney, Michael S. ^{[1
,2
]}

Shukla, Sachet A. ^{[1
,3
]}

Wu, Catherine J. ^{[1
,3
,4
]}

Getz, Gad ^{[1
,5
,6
]}

Hacohen, Nir ^{[1
,4
,7
,8
]}

机构：

[1] Broad Inst, Cambridge, MA 02142 USA

[2] Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02141 USA

[3] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA

[4] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA

[5] Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA

[6] Massachusetts Gen Hosp, Dept Pathol, Charlestown, MA 02129 USA

[7] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Charlestown, MA 02129 USA

[8] Massachusetts Gen Hosp, Dept Med, Charlestown, MA 02129 USA

来源：

CELL | 2015年 / 160卷 / 1-2期

关键词：

CASEIN KINASE-II; T-CELLS; INDUCED APOPTOSIS; CANCER-CELLS; DOWN-REGULATION; EXPRESSION; SURVIVAL; RESISTANCE; LANDSCAPE; MELANOMA;

D O I：

10.1016/j.cell.2014.12.033

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

How the genomic landscape of a tumor shapes and is shaped by anti-tumor immunity has not been systematically explored. Using large-scale genomic data sets of solid tissue tumor biopsies, we quantified the cytolytic activity of the local immune infiltrate and identified associated properties across 18 tumor types. The number of predicted MHC Class I-associated neoantigens was correlated with cytolytic activity and was lower than expected in colorectal and other tumors, suggesting immune-mediated elimination. We identified recurrently mutated genes that showed positive association with cytolytic activity, including beta-2-microglobulin (B2M), HLA-A, -B and -C and Caspase 8 (CASP8), highlighting loss of antigen presentation and blockade of extrinsic apoptosis as key strategies of resistance to cytolytic activity. Genetic amplifications were also associated with high cytolytic activity, including immunosuppressive factors such as PDL1/2 and ALOX12B/15B. Our genetic findings thus provide evidence for immunoediting in tumors and uncover mechanisms of tumor-intrinsic resistance to cytolytic activity.

引用

页码：48 / 61

页数：14

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