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Marco Donia: Biomarkers for immune checkpoint inhibitors – a clinical update
Apr 25, 2025, 18:06

Marco Donia: Biomarkers for immune checkpoint inhibitors – a clinical update

Marco Donia, Research Group Leader of the TIL group at CCIT (Center for Cancer Immune Therapy) and Professor at the University of Copenhagen, shared a post on LinkedIn about a paper by Stephen Wang and Timothy Chan published in Cancer Cell:

“Biomarkers for immune checkpoint inhibitors – a clinical update

Over the past decade, immune checkpoint inhibitors (ICIs) have reshaped oncology. Yet, only a subset of patients benefits. Biomarkers can help better understand which patients are most likely to respond.

FDA-approved biomarkers:

  1. PD-L1 expression: Still the most widely used, though with notable limitations due to heterogeneity and assay variability. Multiple assays exist with varying cutoffs (e.g., TPS, CPS) and antibodies (e.g., 22C3, 28-8, SP142).
  2. Tumor mutational burden (TMB): Approved as a tumor-agnostic biomarker, defined as >10 mutations/Mb.
  3. MSI-high/dMMR status: tumors with strongly increased mutational signatures and often respond well to ICIs.

Emerging Biomarkers:

  1. Clonal TMB
  2. Gene signatures (e.g., IFN-g signature)
  3. Quantification and phenotype of cells in the tumor immune microenvironment
  4. Tumor extrinsic factors (e.g. Microbiome influencers)

Take-home messages:

  1. No single biomarker captures the complexity of ICI response – integrated models are needed.
  2. Biological insights from genomics, transcriptomics, and immunology are transforming clinical strategies.

Clinical Implications: Simple-to-measure biomarkers are still the most clinically useful. Emerging biomarkers may improve prediction strategies.”

“Navigating established and emerging biomarkers for immune checkpoint inhibitor therapy”

Authors: Stephen Wang, Timothy Chan.

Marco Donia: Biomarkers for immune checkpoint inhibitors - a clinical update

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