| Autor: |
Pantazaka E; Laboratory of Biochemistry/Metastatic Signaling, Section of Genetics, Cell Biology and Development, Department of Biology, University of Patras, 26504 Patras, Greece., Ntzifa A; Analysis of Circulating Tumor Cells Lab, Lab of Analytical Chemistry, Department of Chemistry, National and Kapodistrian University of Athens, 15771 Athens, Greece., Roumeliotou A; Laboratory of Biochemistry/Metastatic Signaling, Section of Genetics, Cell Biology and Development, Department of Biology, University of Patras, 26504 Patras, Greece., Lianidou E; Analysis of Circulating Tumor Cells Lab, Lab of Analytical Chemistry, Department of Chemistry, National and Kapodistrian University of Athens, 15771 Athens, Greece., Georgoulias V; Hellenic Oncology Research Group, 11526 Athens, Greece., Kotsakis A; Department of Medical Oncology, University General Hospital of Larisa, 41334 Larisa, Greece., Kallergi G; Laboratory of Biochemistry/Metastatic Signaling, Section of Genetics, Cell Biology and Development, Department of Biology, University of Patras, 26504 Patras, Greece. |
| Abstrakt: |
The PD-1/PD-L1 axis provides CTCs an escape route from the immune system. Phosphorylation of the ribosomal protein S6 is implicated in the same pathway, following mTOR activation. The aim of the study was to investigate the expression of PD-L1 and pS6 in CTCs from NSCLC patients under Osimertinib treatment at a single cell level. CTCs were isolated using ISET from NSCLC patients’ blood [37 at baseline, 25 after the 1st cycle, and 23 at the end of treatment (EOT)]. Staining was performed using immunofluorescence. Cytokeratin-positive (CK+) CTCs were detected in 62% of patients. CK+PD-L1+CD45− and CK+pS6+ phenotypes were detected in 38% and 41% of the patients at baseline, in 28% and 32% after 1st cycle, and in 30% and 35% at EOT, respectively. Spearman’s analysis revealed statistically significant correlations between PD-L1 and pS6 phenotypes at all time points. Survival analysis revealed that CK+pS6+ (p = 0.003) and CKlowpS6+ (p = 0.021) phenotypes after 1st cycle were related to significantly decreased one-year progression-free survival (PFS12m) and PFS, respectively. CK+PD-L1+CD45−phenotype at baseline and after 1st cycle showed a trend for decreased PFS12m. Increased expression of PD-L1/pS6 in CTCs of Osimertinib-treated NSCLC patients implies the activation of the corresponding pathway, which is potentially associated with poor clinical outcomes. |
