1. PD-L1 Expression in Circulating Tumor Cells as a Promising Prognostic Biomarker in Advanced Non–small-cell Lung Cancer Treated with Immune Checkpoint Inhibitors
- Author
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Michelangelo Fiorentino, Filippo Gustavo Dall'Olio, Rita Golfieri, Laura Marcolin, Benedetta Fragomeno, Giada Grilli, Giulia Manferrari, Andrea Ardizzoni, Francesca Sperandi, Mario Terracciano, Nastassja Tober, Francesco Gelsomino, Nicole Conci, Francesca Fontana, Andrea De Giglio, Stefano Brocchi, Dall'Olio F.G., Gelsomino F., Conci N., Marcolin L., De Giglio A., Grilli G., Sperandi F., Fontana F., Terracciano M., Fragomeno B., Tober N., Manferrari G., Brocchi S., Golfieri R., Fiorentino M., and Ardizzoni A.
- Subjects
Male ,0301 basic medicine ,Pulmonary and Respiratory Medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,Immune Checkpoint ,NSCLC ,Predictive ,B7-H1 Antigen ,03 medical and health sciences ,0302 clinical medicine ,Circulating tumor cell ,Advanced cancer ,Carcinoma, Non-Small-Cell Lung ,Internal medicine ,PD-1 ,Biomarkers, Tumor ,Clinical endpoint ,medicine ,Humans ,Prospective Studies ,Lung cancer ,Immune Checkpoint Inhibitors ,Aged ,Aged, 80 and over ,biology ,business.industry ,Hazard ratio ,Cancer ,Middle Aged ,medicine.disease ,CTC ,Immune checkpoint ,030104 developmental biology ,030220 oncology & carcinogenesis ,biology.protein ,Biomarker (medicine) ,Female ,Antibody ,business - Abstract
Background: Circulating tumor cells (CTCs) are a promising source of biological information in cancer. Data correlating PD-L1 expression in CTCs with patients’ response to immune checkpoint inhibitors (ICIs) in non–small-cell lung cancer (NSCLC) are still lacking. Methods: This is a prospective single-center cohort study enrolling patients with advanced NSCLC. CTCs were identified and counted with the CellSearch system. PD-L1 expression on CTCs was assessed with phycoerythrin-conjugated anti-human PD-L1 antibody, clone MIH3 (BioLegend, USA). Primary endpoint was the correlation between the CTCs PD-L1 expression and overall survival (OS). Among secondary objectives, we evaluated the correlation between PD-L1 expression on CTCs and matched tumor tissue and the correlation of CTC number and baseline tumor size (BTS). Results: Thirty-nine patients treated with anti-PD-1/PD-L1 agents as second- or third-line therapy were enrolled. Patients were divided into 3 groups: no CTC detectable (CTCnull, n = 15), PD-L1 positive CTC (CTCpos, n = 13), and PD-L1 negative CTC (CTCneg, n = 11). Median OS in patients with CTCneg was 2.2 months, 95% confidence interval (CI), 0.8-3.6 (reference) versus 3.7 months, 95% CI, 0.1-7.5 (hazard ratio [HR] 0.33; 95% CI, 0.13-0.83; P = .019) in patients with CTCpos versus 16.0 months, 95% CI, 2.2-29.8 (HR 0.17; 95% CI, 0.06-0.45; P< .001) in patients with CTCnull. No correlation was found between PD-L1 expression on CTCs and on tumor tissue. CTC number was correlated with BTS. Conclusion: PD-L1 expression on CTCs is a promising biomarker in patients with NSCLC treated with ICIs. Further validation as predictive biomarker is needed.
- Published
- 2021
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