Germinal immunogenetics as a predictive factor for immunotherapy

Crit Rev Oncol Hematol. 2019 Sep:141:146-152. doi: 10.1016/j.critrevonc.2019.06.013. Epub 2019 Jun 28.

Abstract

Clinical response to checkpoint inhibitors-based (CPIs) therapies can vary among tumor types and between patients. This led to a significant amount of pre-clinical and clinical research into biomarker identification. Biomarkers have been found to cover both the tumor itself and the tumor microenvironment. Entering host-related parameters into the equation should provide a valuable strategy for identifying not only factors predictive of treatment efficacy but also of treatment-related toxicity. It is clear that germline variants can offer efficient and easily-assessable indicators (blood DNA) to enlarge the spectrum of predictive markers for CPI-based treatment. A major issue concerns the real functional significance of the reported single-nucleotide polymorphisms (SNPs) linked to CPI-treatment outcome. Powered calculations should lead to an optimal trade-off between sample size and allele frequency. New molecular technologies and new analytical methods should provide opportunities to bridge the knowledge gap between SNP-CPI treatment associations and the functional impact of these SNPs.

Keywords: Check-point inhibitors; Germinal immunogenetics; Immunotherapy; Predictive factors.

Publication types

  • Review

MeSH terms

  • DNA Mutational Analysis / methods
  • Drug Resistance, Neoplasm / genetics*
  • Drug Resistance, Neoplasm / immunology
  • Germ-Line Mutation / physiology*
  • Humans
  • Immunogenetics / methods*
  • Immunologic Factors / therapeutic use
  • Immunotherapy* / methods
  • Neoplasms / diagnosis*
  • Neoplasms / immunology
  • Neoplasms / therapy*
  • Pharmacogenomic Testing / methods
  • Prognosis
  • Treatment Outcome
  • Tumor Microenvironment / genetics
  • Tumor Microenvironment / immunology

Substances

  • Immunologic Factors