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Review
. 2017 Feb 9;168(4):600-612.
doi: 10.1016/j.cell.2017.01.014.

Applications of Immunogenomics to Cancer

Affiliations
Review

Applications of Immunogenomics to Cancer

X Shirley Liu et al. Cell. .

Abstract

Cancer immunogenomics originally was framed by research supporting the hypothesis that cancer mutations generated novel peptides seen as "non-self" by the immune system. The search for these "neoantigens" has been facilitated by the combination of new sequencing technologies, specialized computational analyses, and HLA binding predictions that evaluate somatic alterations in a cancer genome and interpret their ability to produce an immune-stimulatory peptide. The resulting information can characterize a tumor's neoantigen load, its cadre of infiltrating immune cell types, the T or B cell receptor repertoire, and direct the design of a personalized therapeutic.

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Figures

Fig 1
Fig 1. An Overall Workflow for Neoantigen Discovery and Personalized Cancer Vaccine Design
Starting from next-generation sequencing of DNA exomes to compare tumor to normal DNA, and of tumor RNA to evaluate gene expression, this figure illustrates the steps outlined in the primer to identify tumor-specific mutant antigens (neoantigens) from NGS data, to evaluate the neoantigens, and to design a personalized neoantigen vaccine.
Figure 2
Figure 2. Idealized Selection of Mutant-Containing Peptides for Neoantigen Prediction
(A) The localized peptides that tile across and contain the mutated amino acid substitution are identified and parsed into the neoantigen prediction pipeline. Each peptide is considered for HLA binding strength relative to its non-mutant (wild-type) counterpart. (B) Shown is the top scoring candidate peptide that was selected across all specified k-mers and between all HLA types that were input to the neoantigen prediction pipeline.
Fig 3
Fig 3. Structure and Diversity in the T Cell Receptor
(A) The mature T cell heterodimer, consisting of α- and β-subunit chains. The α subunit chains consist of variable (V), joining (J), and constant (C) regions, whereas the β subunit includes an additional diversity (D) region. (B) V-D-J recombination and post-transcriptional processing of a TCR-β subunit chain.

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