Genomic Correlates of Immune-Cell Infiltrates in Colorectal Carcinoma
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Author(s)
Giannakis, Marios
Mu, Xinmeng Jasmine
Shukla, Sachet A.
Qian, Zhi Rong
Cohen, Ofir
Nishihara, Reiko
Bahl, Samira
Cao, Yin
Amin-Mansour, Ali
Yamauchi, Mai
Date Issued
April 2016
Journal
Cell Reports
Publisher
Elsevier
Citation
Giannakis, Marios et al. “Genomic Correlates of Immune-Cell Infiltrates in Colorectal Carcinoma.” Cell Reports 15, 4 (April 2016): 857–865 © 2016 The Authors
Version
Final published version
Abstract
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.
MIT Department
Massachusetts Institute of Technology. Department of Biology
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Creative Commons Attribution 4.0 International License
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DOI of Published Version
https://doi.org/10.1016/J.CELREP.2016.03.075
