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Updated: Oct 2, 2025
Monitoring PD-1-Blocking Antibodies Bound to T Cells Derived from a Drop of Peripheral Blood
Published on: February 5, 2020
Biomarkers of response to PD-1 pathway blockade
Hanxiao Li1, P Anton van der Merwe2, Shivan Sivakumar3
1Green Templeton College, University of Oxford, Oxford, UK. lisa.li@ouh.nhs.uk.
Abstract:
The binding of T cell immune checkpoint proteins programmed death 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) to their ligands allows immune evasion by tumours. The development of therapeutic antibodies, termed checkpoint inhibitors, that bind these molecules or their ligands, has provided a means to release this brake on the host anti-tumour immune response. However, these drugs are costly, are associated with potentially severe side effects, and only benefit a small subset of patients. It is therefore important to identify biomarkers that discriminate between responders and non-responders. This review discusses the determinants for a successful response to antibodies that bind PD-1 or its ligand PD-L1, dividing them into markers found in the tumour biopsy and those in non-tumour samples. It provides an update on the established predictive biomarkers (tumour PD-L1 expression, tumour mismatch repair deficiency and tumour mutational burden) and assesses the evidence for new potential biomarkers.
Insights
Identifying biomarkers is crucial for predicting patient response to immune checkpoint inhibitors targeting programmed death 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). This review examines established and emerging predictive biomarkers for these cancer immunotherapies.
Area of Science:
- Immunology
- Oncology
- Pharmacology
Background:
- Tumors evade immune responses through checkpoint proteins like PD-1 and CTLA-4.
- Checkpoint inhibitors are therapeutic antibodies that block these proteins, enhancing anti-tumor immunity.
- Current limitations include high cost, severe side effects, and limited efficacy in a subset of patients.
Purpose of the Study:
- To review and update knowledge on biomarkers predicting response to PD-1/PD-L1 targeting antibodies.
- To differentiate between biomarkers found in tumor biopsies versus non-tumor samples.
- To assess established and emerging predictive biomarkers for cancer immunotherapy.
Main Methods:
- Literature review focusing on predictive biomarkers for PD-1/PD-L1 inhibitors.
- Categorization of biomarkers into tumor-based and non-tumor-based.
- Assessment of evidence for established and novel predictive markers.
Main Results:
- Established biomarkers include tumor PD-L1 expression, mismatch repair deficiency, and tumor mutational burden.
- Discussion includes biomarkers from both tumor biopsies and peripheral samples.
- Evidence for new potential biomarkers is evaluated.
Conclusions:
- Accurate biomarker identification is essential for optimizing checkpoint inhibitor therapy.
- A combination of biomarkers may improve patient stratification.
- Further research into novel biomarkers is warranted to expand treatment benefits.
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