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Emerging biomarkers for immune checkpoint inhibition in lung cancer
1Perlmutter Cancer Center, NYU Langone Health, United States.
Abstract:
Immune checkpoint inhibition with anti-PD-1 therapy has been notably successful in non-small cell lung cancer (NSCLC) and changed standard practice in multiple settings. However, despite some durable benefits seen, the majority of unselected patients with NSCLC fail to respond to checkpoint inhibitors. Patient selection is crucial and will become even more important in the development of combination therapies with immune checkpoint inhibitors. PD-L1 expression by immunohistochemistry (IHC) has emerged as the most commonly used clinical biomarker of response and overall tumor mutational burden (TMB) is being explored as a clinical biomarker. However, both are hampered by being imperfect predictors of response and both can be dynamic during the course of illness. In this review, we will discuss the development of PD-L1 expression as a biomarker as well as the ongoing emergence of other genomic and proteomic markers that can help refine our use of immunotherapies to maximize benefit in the most patients.
Insights
Immune checkpoint inhibitors show promise in non-small cell lung cancer (NSCLC), but most patients do not respond. Biomarkers like PD-L1 expression and tumor mutational burden (TMB) are imperfect, necessitating new strategies for patient selection.
Area of Science:
- Oncology
- Immunology
- Biomarker Discovery
Background:
- Anti-PD-1 therapy has transformed non-small cell lung cancer (NSCLC) treatment.
- However, a significant proportion of NSCLC patients do not respond to immune checkpoint inhibitors.
- Effective patient selection is critical for optimizing immunotherapy outcomes and developing combination strategies.
Purpose of the Study:
- To review the evolution of PD-L1 expression as a biomarker for anti-PD-1 therapy in NSCLC.
- To explore emerging genomic and proteomic markers for improved patient stratification.
- To enhance the efficacy of immunotherapies by identifying predictive biomarkers.
Main Methods:
- Review of current literature on biomarkers in NSCLC immunotherapy.
- Analysis of PD-L1 expression by immunohistochemistry (IHC) as a clinical biomarker.
- Exploration of tumor mutational burden (TMB) and other novel biomarkers.
Main Results:
- PD-L1 IHC is the primary biomarker but has limitations in predicting response.
- Tumor mutational burden (TMB) is under investigation but also imperfect.
- Biomarker performance can be dynamic and influenced by disease progression.
Conclusions:
- Refining patient selection for anti-PD-1 therapy in NSCLC is essential.
- Novel genomic and proteomic biomarkers are needed to complement PD-L1.
- Accurate biomarker strategies will maximize immunotherapy benefits for more NSCLC patients.
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