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Cancer Immunotherapy with Immune Checkpoint Inhibitors-Biomarkers of Response and Toxicity; Current Limitations and

Brian Healey Bird1,2, Ken Nally3,4, Karine Ronan5

  • 1School of Medicine, University College Cork, T12 K8AF Cork, Ireland.

Diagnostics (Basel, Switzerland)
|January 21, 2022
PubMed

Insights

Immune checkpoint inhibitors improve cancer treatment but benefit less than 40% of patients. This review explores emerging biomarkers, including the microbiome, to predict response and reduce side effects.

Area of Science:

  • Oncology
  • Immunology
  • Biomarker Discovery

Background:

  • Immune checkpoint inhibitors (ICIs) are revolutionary cancer therapies, significantly improving patient survival and quality of life.
  • Despite their success, ICI efficacy is limited to under 40% of patients, even in responsive cancers like melanoma, and they are associated with significant autoimmune toxicities.
  • Current licensed biomarkers, including Programmed Death Ligand 1 (PD-L1) expression, microsatellite instability (MSI), and tumor mutational burden (TMB), lack sufficient sensitivity and specificity for predicting treatment response.

Purpose of the Study:

  • To review emerging biomarkers for predicting response and toxicity to immune checkpoint inhibitors.
  • To discuss novel tissue-based and liquid biomarkers beyond current standards.
  • To explore the role of the fecal microbiome in modulating ICI treatment outcomes.

Main Methods:

  • Literature review of emerging biomarkers for immune checkpoint inhibitor therapy.
  • Analysis of novel immunohistochemistry scoring systems.
  • Examination of gene expression profiling in tumors, stroma, and immune cells.
  • Evaluation of liquid biomarkers including inflammatory markers, kynurenine/tryptophan ratio, circulating immune cells, cytokines, and cell-free DNA.
  • Review of studies investigating the fecal microbiome's impact on ICI efficacy and toxicity.

Main Results:

  • Current biomarkers for ICIs show limited predictive power.
  • Emerging biomarkers, including novel IHC scores, gene expression profiles (tumor, stromal, immune), and various liquid biomarkers, show promise.
  • The fecal microbiome is increasingly recognized as a significant factor influencing patient response and the development of adverse events.
  • A multi-omic approach integrating various biomarkers may improve prediction of ICI outcomes.

Conclusions:

  • There is a critical need for more sensitive and specific biomarkers to optimize immune checkpoint inhibitor therapy.
  • Emerging tissue, liquid, and microbiome-based biomarkers offer potential for improved patient stratification and personalized treatment strategies.
  • Further research into these novel biomarkers is essential to enhance clinical decision-making and improve patient outcomes in cancer immunotherapy.
Keywords:
biomarkercancercytokineflow cytometryimmunotherapymicrobiomemicroenvironment

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