Genomic Correlates of Immune-Cell Infiltrates in Colorectal Carcinoma

被引：638

作者：

Giannakis, Marios ^{[1
,2
,3
]}

Mu, Xinmeng Jasmine ^{[1
,2
,3
]}

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

Qian, Zhi Rong ^{[1
]}

Cohen, Ofir ^{[1
,3
]}

Nishihara, Reiko ^{[1
,4
,5
,6
]}

Bahl, Samira ^{[3
,5
]}

Cao, Yin ^{[7
,8
]}

Amin-Mansour, Ali ^{[1
,3
]}

Yamauchi, Mai ^{[1
]}

Sukawa, Yasutaka ^{[9
]}

Stewart, Chip ^{[3
]}

Rosenberg, Mara ^{[3
]}

Mima, Kosuke ^{[1
]}

Inamura, Kentaro ^{[1
]}

Nosho, Katsuhiko ^{[10
]}

Nowak, Jonathan A. ^{[11
]}

Lawrence, Michael S. ^{[3
]}

Giovannucci, Edward L. ^{[4
,5
,12
]}

Chan, Andrew T. ^{[7
,8
,12
]}

Ng, Kimmie ^{[1
,2
]}

Meyerhardt, Jeffrey A. ^{[1
,2
]}

Van Allen, Eliezer M. ^{[1
,2
,3
]}

Getz, Gad ^{[3
,13
]}

Gabriel, Stacey B. ^{[3
]}

Lander, Eric S. ^{[3
,14
,15
]}

Wu, Catherine J. ^{[2
,3
]}

Fuchs, Charles S. ^{[1
,2
,12
]}

Ogino, Shuji ^{[1
,4
,11
]}

Garraway, Levi A. ^{[1
,2
,3
]}

机构：

[1] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA

[2] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02215 USA

[3] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA

[4] Harvard Univ, TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA

[5] Harvard Univ, TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA

[6] Harvard Univ, TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA

[7] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Gastroenterol, Boston, MA 02114 USA

[8] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Clin & Translat Epidemiol Unit, Boston, MA 02114 USA

[9] Keio Univ, Sch Med, Div Internal Med, Dept Gastroenterol & Hepatol, Tokyo 1088345, Japan

[10] Sapporo Med Univ, Dept Gastroenterol Rheumatol & Clin Immun, Sch Med, Sapporo, Hokkaido 0608543, Japan

[11] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div MPE Mol Pathol Epidemiol,Dept Pathol, Boston, MA 02115 USA

[12] Harvard Univ, Sch Med, Brigham & Womens Hosp, Channing Div Network Med,Dept Med, Boston, MA 02115 USA

[13] Harvard Univ, Sch Med, Ctr Canc, Massachusetts Gen Hosp, Boston, MA 02114 USA

[14] MIT, Dept Biol, 77 Massachusetts Ave, Cambridge, MA 02139 USA

[15] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA

来源：

CELL REPORTS | 2016年 / 15卷 / 04期

关键词：

CANCER; MUTATION; NEOANTIGENS; ANTIGENS; SURVIVAL; ASPIRIN; TUMORS;

D O I：

10.1016/j.celrep.2016.03.075

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Large-scale genomic characterization of tumors from prospective cohort studies may yield new insights into cancer pathogenesis. We performed whole-exome sequencing of 619 incident colorectal cancers (CRCs) and integrated the results with tumor immunity, pathology, and survival data. We identified recurrently mutated genes in CRC, such as BCL9L, RBM10, CTCF, and KLF5, that were not previously appreciated in this disease. Furthermore, we investigated the genomic correlates of immune-cell infiltration and found that higher neoantigen load was positively associated with overall lymphocytic infiltration, tumor-infiltrating lymphocytes (TILs), memory T cells, and CRC-specific survival. The association with TILs was evident even within microsatellite-stable tumors. We also found positive selection of mutations in HLA genes and other components of the antigen-processing machinery in TIL-rich tumors. These results may inform immunotherapeutic approaches in CRC. More generally, this study demonstrates a framework for future integrative molecular epidemiology research in colorectal and other malignancies.

引用

页码：857 / 865

页数：9

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