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PD-L1 and epithelial-mesenchymal transition in circulating tumor cells from non-small cell lung cancer patients: A
Cristina Raimondi1, Guido Carpino2, Chiara Nicolazzo1
1Dipartimento di Medicina Molecolare, Sapienza Università di Roma Roma, Italia.
Abstract:
The programmed cell death 1 (PD-1)/PD-1 ligand 1 (PD-L1) pathway has emerged as a critical inhibitory pathway regulating T-cell response in non-small-cell lung cancer (NSCLC), and the development of PD-1/PD-L1 inhibitors has changed the landscape of NSCLC therapy. Nevertheless, the high degree of non-responders demonstrates that we are still far from completely understanding the events underlying tumor immune resistance. Although the expression of PD-L1 in tumor tissue has been correlated with clinical response to anti PD-1 inhibitors, the ability of this marker to discriminate the subgroup of patients who derive benefit from immunotherapy is suboptimal. Circulating tumor cells (CTCs), as an accessible source of tumor for biologic characterization that can be serially obtained with minimally invasive procedure, hold significant promise to facilitate treatment-specific biomarkers discovery. We recently demonstrated that the presence of PD-L1 on CTCs apparently predicts resistance to the anti-PD-1 Nivolumab in metastatic NSCLC patients and that PD-L1 positive CTCs usually have an elongated morphology that can be ascribed to epithelial-mesenchymal transition (EMT). We here demonstrate for the first time that PD-L1 positive CTCs isolated from NSCLC patients are characterized by partial EMT phenotype, and hypothesize that the co-expression of PD-L1 and EMT markers might represent for these cells a possible molecular background for immune escape.
Insights
Programmed cell death 1 (PD-1) and its ligand (PD-L1) are key in non-small-cell lung cancer (NSCLC) immune resistance. PD-L1 positive circulating tumor cells (CTCs) with partial epithelial-mesenchymal transition (EMT) may indicate immune escape in NSCLC patients.
Area of Science:
- Oncology
- Immunology
- Cancer Biology
Background:
- The programmed cell death 1 (PD-1)/PD-1 ligand 1 (PD-L1) pathway is crucial for T-cell regulation in non-small-cell lung cancer (NSCLC).
- While PD-1/PD-L1 inhibitors have advanced NSCLC therapy, many patients do not respond, highlighting unmet needs in understanding tumor immune resistance.
- PD-L1 expression in tumor tissue is an imperfect biomarker for predicting response to anti-PD-1 immunotherapy.
Purpose of the Study:
- To investigate the phenotype of PD-L1 positive circulating tumor cells (CTCs) in NSCLC patients.
- To explore the association between PD-L1 expression on CTCs and epithelial-mesenchymal transition (EMT).
- To determine if PD-L1 and EMT co-expression on CTCs contribute to immune escape in NSCLC.
Main Methods:
- Isolation and characterization of circulating tumor cells (CTCs) from NSCLC patients.
- Assessment of PD-L1 expression on CTCs.
- Evaluation of epithelial-mesenchymal transition (EMT) markers on PD-L1 positive CTCs.
Main Results:
- PD-L1 positive CTCs isolated from NSCLC patients exhibit a partial EMT phenotype.
- This partial EMT phenotype in PD-L1 positive CTCs is characterized by elongated cell morphology.
- The co-expression of PD-L1 and EMT markers on CTCs is demonstrated for the first time in NSCLC.
Conclusions:
- PD-L1 positive CTCs in NSCLC patients display a partial EMT phenotype.
- This phenotype may represent a mechanism for immune escape in NSCLC.
- Targeting PD-L1 and EMT pathways in CTCs could offer new therapeutic strategies for NSCLC.
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