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Is the Blood an Alternative for Programmed Cell Death Ligand 1 Assessment in Non-Small Cell Lung Cancer?
Emmanuel Acheampong1, Isaac Spencer1, Weitao Lin1
1School of Medical and Health Sciences, Edith Cowan University, 270 Joondalup Drive, Joondalup, WA 6027, Australia.
Abstract:
Anti-programmed cell death (PD)-1/PD-ligand 1 (L1) therapies have significantly improved the outcomes for non-small cell lung cancer (NSCLC) patients in recent years. These therapies work by reactivating the immune system and enabling it to target cancer cells once more. There is a general agreement that expression of PD-L1 on tumour cells predicts the therapeutic response to PD-1/PD-L1 inhibitors in NSCLC. Hence, immunohistochemical staining of tumour tissue biopsies from NSCLC patients with PD-L1 antibodies is the current standard used to aid selection of patients for treatment with anti-PD-1 as first line therapy. However, issues of small tissue samples, tissue heterogeneity, the emergence of new metastatic sites, and dynamic changes in the expression of PD-L1 may influence PD-L1 status during disease evolution. Re-biopsy would expose patients to the risk of complications and tardy results. Analysis of PD-L1 expression on circulating tumour cells (CTCs) may provide an accessible and non-invasive means to select patients for anti-PD-1 therapies. Additionally, CTCs could potentially provide a useful biomarker in their own right. Several published studies have assessed PD-L1 expression on CTCs from NSCLC patients. Overall, analysis of PD-L1 on CTCs is feasible and could be detected prior to and after frontline therapy. However, there is no evidence on whether PD-L1 expression on CTCs could predict the response to anti-PD-1/PD-L1 treatment. This review examines the challenges that need to be addressed to demonstrate the clinical validity of PD-L1 analysis in CTCs as a biomarker capable of predicting the response to immune checkpoint blockade.
Insights
Analyzing programmed cell death ligand 1 (PD-L1) on circulating tumor cells (CTCs) offers a less invasive method for non-small cell lung cancer (NSCLC) treatment selection. Further research is needed to confirm if PD-L1 on CTCs can predict response to anti-PD-1/PD-L1 therapies.
Area of Science:
- Oncology
- Immunology
- Biomarker Discovery
Background:
- Anti-programmed cell death (PD)-1/PD-ligand 1 (L1) immunotherapies have transformed non-small cell lung cancer (NSCLC) treatment.
- Tumor cell PD-L1 expression is the current standard for predicting response to these therapies.
- Limitations of tumor biopsies, including heterogeneity and invasiveness, necessitate alternative biomarkers.
Purpose of the Study:
- To review the feasibility and potential of analyzing PD-L1 expression on circulating tumor cells (CTCs) in NSCLC.
- To explore the challenges in validating PD-L1 on CTCs as a predictive biomarker for anti-PD-1/PD-L1 therapy response.
Main Methods:
- Review of published studies assessing PD-L1 expression on CTCs in NSCLC patients.
- Discussion of technical and clinical challenges in CTC analysis.
- Examination of the potential for CTCs as a non-invasive biomarker.
Main Results:
- PD-L1 expression analysis on CTCs is feasible and detectable before and after treatment.
- CTCs may offer an accessible, non-invasive alternative to tumor biopsies for monitoring PD-L1 status.
- Current evidence does not establish whether PD-L1 on CTCs predicts treatment response.
Conclusions:
- PD-L1 analysis on CTCs shows promise as a non-invasive biomarker in NSCLC.
- Addressing challenges in clinical validation is crucial for integrating PD-L1 CTC analysis into treatment selection.
- Further research is required to demonstrate the predictive value of PD-L1 on CTCs for anti-PD-1/PD-L1 therapy efficacy.
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