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Biomarkers for immune checkpoint inhibition in non-small cell lung cancer (NSCLC)
J Nicholas Bodor1, Yanis Boumber1,2,3, Hossein Borghaei1,2
1Department of Hematology/Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania.
Abstract:
The emergence of immunotherapy has dramatically changed how non-small cell lung cancer is treated, and longer survival is now possible for some patients, even those with advanced disease. Although some patients achieve durable responses to checkpoint blockade, not all experience such benefits, and some suffer from significant immunotoxicities. Given this, biomarkers that predict response to therapy are essential, and testing for tumor programmed death ligand 1(PD-L1) expression is the current standard. The extent of PD-L1 expression determined by immunohistochemistry (IHC) has demonstrated a correlation with treatment response, although limitations with this marker exist. Recently, tumor mutational burden has emerged as an alternative biomarker, and studies have demonstrated its utility, irrespective of the PD-L1 level of a tumor. Gene expression signatures, tumor genotype (such as the presence of an oncogenic driver mutation), as well as the density of tumor-infiltrating lymphocytes in the tumor microenvironment also seem to affect response to immunotherapy and are being researched. Peripheral serum markers are being studied, and some have demonstrated predictive ability, although most are still investigational and need prospective validation. In the current article, the authors review the biomarker PD-L1 as well as other emerging and investigational tissue-based and serum-based markers that have potential to better predict responders to immunotherapy.
Insights
Predicting immunotherapy response in non-small cell lung cancer is crucial. This review explores programmed death ligand 1 (PD-L1) and emerging biomarkers to identify patients who will benefit from treatment.
Area of Science:
- Oncology
- Immunology
- Biomarker Research
Background:
- Immunotherapy has revolutionized non-small cell lung cancer (NSCLC) treatment, offering prolonged survival for some patients.
- Despite advances, not all patients respond to checkpoint blockade, and some experience severe immune-related toxicities.
- Accurate prediction of treatment response is vital for optimizing patient outcomes.
Purpose of the Study:
- To review current and emerging biomarkers for predicting immunotherapy response in NSCLC.
- To discuss the limitations of existing biomarkers and the potential of novel approaches.
Main Methods:
- Review of existing literature on biomarkers for immunotherapy in NSCLC.
- Analysis of programmed death ligand 1 (PD-L1) expression as a standard biomarker.
- Exploration of emerging tissue-based (tumor mutational burden, gene expression, tumor genotype, tumor-infiltrating lymphocytes) and serum-based markers.
Main Results:
- Programmed death ligand 1 (PD-L1) expression via immunohistochemistry (IHC) is the current standard but has limitations.
- Tumor mutational burden shows promise as a predictive biomarker, independent of PD-L1 levels.
- Other investigational markers, including gene expression signatures, tumor genotype, tumor-infiltrating lymphocytes, and peripheral serum markers, are under active research.
Conclusions:
- Accurate prediction of immunotherapy response in NSCLC requires a multi-faceted biomarker approach.
- Emerging tissue-based and serum-based markers hold significant potential to improve patient selection for immunotherapy.
- Further prospective validation of investigational biomarkers is necessary to refine clinical application.
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