Importance of immunopharmacogenomics in cancer treatment: Patient selection and monitoring for immune checkpoint antibodies

Cancer Sci. 2016 Feb;107(2):107-15. doi: 10.1111/cas.12862.

Abstract

In the last 5 years, immune checkpoint antibodies have become established as anticancer agents for various types of cancer. These antibody drugs, namely cytotoxic T-lymphocyte-associated antigen, programmed death-1, and programmed death ligand-1 antibodies, have revealed relatively high response rates, the ability to induce durable responses, and clinical efficacy in malignancies not previously thought to be susceptible to immune-based strategies. However, because of its unique mechanisms of activating the host immune system against cancer as well as expensive cost, immune checkpoint blockade faces novel challenges in selecting appropriate patient populations, monitoring clinical responses, and predicting immune adverse events. The development of objective criteria for selecting patient populations that are likely to have benefit from these therapies has been vigorously investigated but still remains unclear. In this review, we describe immune checkpoint inhibition-specific challenges with patient selection and monitoring, and focus on approaches to remedy these challenges. We also discuss applications of the emerging field of immunopharmacogenomics for guiding selection and monitoring for anti-immune checkpoint treatment.

Keywords: Biomarkers; T-cell receptor; checkpoint inhibitors; immunopharmacogenomics; immunotherapy.

Publication types

  • Review

MeSH terms

  • Antibodies, Monoclonal / therapeutic use
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Antineoplastic Agents / therapeutic use*
  • Humans
  • Immunotherapy / methods*
  • Ipilimumab
  • Neoplasms / drug therapy*
  • Neoplasms / genetics*
  • Neoplasms / immunology
  • Nivolumab
  • Patient Selection*
  • Pharmacogenetics

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents
  • Ipilimumab
  • Nivolumab
  • pembrolizumab