Genomic Correlates of Immune-Cell Infiltrates in Colorectal Carcinoma
By M. Giannakis, X. Mu, S. Shukla, Z. Qian, Ofir Cohen, Reiko Nishihara, S. Bahl, Yin Cao, Ali Amin-Mansour, Mai Yamauchi and 20 more. Cell Reports, 2016
908 citations recorded by the source corpus.
Summary 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.
Subfields: Immunology, Oncology, Pathology and Forensic Medicine
View Paper: https://www.semanticscholar.org/paper/62d0bd876267ac203d1415e58cab46ea26d005c0
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In Oncology
Citations in the corpus
- Clinical sequencing defines the genomic landscape of metastatic colorectal cancer (2018, background): “More recently, comprehensive sequencing studies, such as The Cancer Genome Atlas (TCGA) (Cancer Genome Atlas Network, 2012; Giannakis et al., 2016; Haan et al., 2014), have defined molecular subtypes of CRC, by identifying genomic events characteristic of ultramutated, microsatellite…”
- Targeting KRAS Mutant Cancers with a Covalent G12C-Specific Inhibitor. (2018, background): “, 2017), as well as 1%–4% of pancreatic and colorectal adenocarcinomas, respectively (Bailey et al., 2016; Giannakis et al., 2016).”