Determination of PD-L1 Expression in Circulating Tumor Cells of NSCLC Patients and Correlation with Response to PD-1/PD-L1 Inhibitors
AbstractCirculating tumor cells (CTCs) hold great potential to answer key questions of how non-small cell lung cancer (NSCLC) evolves and develops resistance upon anti-PD-1/PD-L1 treatment. Currently, their clinical utility in NSCLC is compromised by a low detection rate with the established, Food and Drug Administration (FDA)-approved, EpCAM-based CellSearch® System. We tested an epitope-independent method (ParsortixTM system) and utilized it to assess PD-L1 expression of CTCs from NSCLC patients. We prospectively collected 127 samples, 97 of which were analyzed with the epitope-independent system in comparison to the CellSearch system. CTCs were determined by immunocytochemistry as intact, nucleated, CD45−, pankeratins (K)+ cells. PD-L1 status of CTCs was evaluated from 89 samples. With the epitope-independent system, ≥1 CTC per blood sample was detected in 59 samples (61%) compared to 31 samples (32%) with the EpCAM-based system. Upon PD-L1 staining, 47% of patients harbored only PD-L1+CTCs, 47% had PD-L1+ and PD-L1−CTCs, and only 7% displayed exclusively PD-L1−CTCs. The percentage of PD-L1+CTCs did not correlate with the percentage of PD-L1+ in biopsies determined by immunohistochemistry (p = 0.179). Upon disease progression, all patients showed an increase in PD-L1+CTCs, while no change or a decrease in PD-L1+CTCs was observed in responding patients (n = 11; p = 0.001). Our data show a considerable heterogeneity in the PD-L1 status of CTCs from NSCLC patients. An increase of PD-L1+CTCs holds potential to predict resistance to PD-1/PD-L1 inhibitors. View Full-Text
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Janning, M.; Kobus, F.; Babayan, A.; Wikman, H.; Velthaus, J.-L.; Bergmann, S.; Schatz, S.; Falk, M.; Berger, L.-A.; Böttcher, L.-M.; Päsler, S.; Gorges, T.M.; O’Flaherty, L.; Hille, C.; Joosse, S.A.; Simon, R.; Tiemann, M.; Bokemeyer, C.; Reck, M.; Riethdorf, S.; Pantel, K.; Loges, S. Determination of PD-L1 Expression in Circulating Tumor Cells of NSCLC Patients and Correlation with Response to PD-1/PD-L1 Inhibitors. Cancers 2019, 11, 835.
Janning M, Kobus F, Babayan A, Wikman H, Velthaus J-L, Bergmann S, Schatz S, Falk M, Berger L-A, Böttcher L-M, Päsler S, Gorges TM, O’Flaherty L, Hille C, Joosse SA, Simon R, Tiemann M, Bokemeyer C, Reck M, Riethdorf S, Pantel K, Loges S. Determination of PD-L1 Expression in Circulating Tumor Cells of NSCLC Patients and Correlation with Response to PD-1/PD-L1 Inhibitors. Cancers. 2019; 11(6):835.Chicago/Turabian Style
Janning, Melanie; Kobus, Franca; Babayan, Anna; Wikman, Harriet; Velthaus, Janna-Lisa; Bergmann, Sonja; Schatz, Stefanie; Falk, Markus; Berger, Lars-Arne; Böttcher, Lisa-Marie; Päsler, Sarina; Gorges, Tobias M.; O’Flaherty, Linda; Hille, Claudia; Joosse, Simon A.; Simon, Ronald; Tiemann, Markus; Bokemeyer, Carsten; Reck, Martin; Riethdorf, Sabine; Pantel, Klaus; Loges, Sonja. 2019. "Determination of PD-L1 Expression in Circulating Tumor Cells of NSCLC Patients and Correlation with Response to PD-1/PD-L1 Inhibitors." Cancers 11, no. 6: 835.
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