Toward in silico Identification of Tumor Neoantigens in Immunotherapy

Trends Mol Med. 2019 Nov;25(11):980-992. doi: 10.1016/j.molmed.2019.08.001. Epub 2019 Sep 4.

Abstract

Cancer immunotherapy includes cancer vaccination, adoptive T cell transfer (ACT) with chimeric antigen receptor (CAR) T cells, and administration of tumor-infiltrating lymphocytes and immune-checkpoint blockade such as anti-CTLA4/anti-PD1 inhibitors that can directly or indirectly target tumor neoantigens and elicit a T cell response. Accurate, rapid, and cost-effective identification of neoantigens, however, is critical for successful immunotherapy. Here, we review computational issues for neoantigen identification by summarizing the various sources of neoantigens and their identification from high-throughput sequencing data. Several opinions are presented to inspire further discussions toward improving neoantigen identification. Continuing efforts are required to improve the sensitivity and specificity of bona fide neoantigens, taking advantage of the development of high-throughput sequencing techniques for effective and personalized cancer immunotherapy.

Keywords: biomarkers; immunotherapy; mass spectrometry; neoantigen identification.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adoptive Transfer / trends
  • Alternative Splicing
  • Antigens, Neoplasm* / genetics
  • Antigens, Neoplasm* / isolation & purification
  • Biomarkers, Tumor
  • CTLA-4 Antigen / immunology
  • CTLA-4 Antigen / metabolism
  • Computer Simulation / trends
  • Gene Expression Profiling
  • Genomics
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Immunotherapy / trends*
  • Immunotherapy, Adoptive / trends
  • Loss of Heterozygosity
  • Major Histocompatibility Complex / genetics
  • Neoplasms / immunology*
  • Neoplasms / therapy
  • Prognosis
  • Programmed Cell Death 1 Receptor / immunology
  • Programmed Cell Death 1 Receptor / metabolism
  • Proteomics
  • T-Lymphocytes / immunology
  • T-Lymphocytes / transplantation

Substances

  • Antigens, Neoplasm
  • Biomarkers, Tumor
  • CTLA-4 Antigen
  • CTLA4 protein, human
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor