Predictive biomarkers for immune checkpoint blockade and opportunities for combination therapies

Hongxing Shen, Eddy Shih Hsin Yang, Marty Conry, John Fiveash, Carlo Contreras, James A. Bonner, Lewis Zhichang Shi

Research output: Contribution to journalReview articlepeer-review

57 Scopus citations

Abstract

Immune checkpoint blockade therapies (ICBs) are a prominent breakthrough in cancer immunotherapy in recent years (named the 2013 “Breakthrough of the Year” by the Science magazine). Thus far, FDA-approved ICBs primarily target immune checkpoints CTLA-4, PD-1, and PD-L1. Notwithstanding their impressive long-term therapeutic benefits, their efficacy is limited to a small subset of cancer patients. In addition, ICBs induce inadvertent immune-related adverse events (irAEs) and can be costly for long-term use. To overcome these limitations, two strategies are actively being pursued: identification of predictive biomarkers for clinical response to ICBs and multi-pronged combination therapies. Biomarkers will allow clinicians to practice a precision medicine approach in ICBs (biomarker-based patient selection) such as treating triple-negative breast cancer patients that exhibit PD-L1 staining of tumor-infiltrating immune cells in ≥1% of the tumor area with nanoparticle albumin-bound (nab)–paclitaxel plus anti-PD-L1 and treating patients of MSI-H or MMR deficient unresectable or metastatic solid tumors with pembrolizumab (anti-PD-1). Importantly, the insights gained from these biomarker studies can guide rational combinatorial strategies such as CDK4/6 inhibitor/fractionated radiotherapy/HDACi in conjunction with ICBs to maximize therapeutic benefits. Further, with the rapid technological advents (e.g., ATCT-Seq), we predict more reliable biomarkers will be identified, which in turn will inspire more promising combination therapies.

Original languageEnglish
Pages (from-to)232-246
Number of pages15
JournalGenes and Diseases
Volume6
Issue number3
DOIs
StatePublished - Sep 2019

Bibliographical note

Publisher Copyright:
© 2019

Keywords

  • IFN-γ
  • Immune checkpoint
  • Microbiota
  • Microsatellite instability
  • Neoantigen
  • PD-L1
  • Radiotherapy

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Genetics(clinical)
  • Cell Biology

Fingerprint

Dive into the research topics of 'Predictive biomarkers for immune checkpoint blockade and opportunities for combination therapies'. Together they form a unique fingerprint.

Cite this