M Ilié1,2,3,4, E Szafer-Glusman5, V Hofman1,2,3,4, E Chamorey6, S Lalvée1,2,3, E Selva1,4, S Leroy7, C-H Marquette7, M Kowanetz5, P Hedge5, E Punnoose5, P Hofman1,2,3,4. 1. University Hospital Federation OncoAge, CHU de Nice, Nice, France. 2. Laboratory of Clinical and Experimental Pathology, Pasteur Hospital, Nice, France. 3. Liquid Biopsy Laboratory, Nice, France. 4. Hospital-Integrated Biobank (BB-0033-00025), Nice, France. 5. Oncology Biomarker Development, GENENTECH Inc., South San Francisco, USA. 6. Biostatistics Unit, Antoine Lacassagne Comprehensive Cancer Center, Nice, France. 7. Department of Pulmonary Medicine and Oncology, University Hospital Federation OncoAge, CHU de Nice, Nice, France.
Abstract
Background: Expression of PD-L1 in tumor cells and tumor-infiltrating immune cells has been associated with improved efficacy to anti-PD-1/PD-L1 inhibitors in patients with advanced-stage non-small-cell lung cancer (NSCLC) and emerged as a potential biomarker for the selection of patients to cancer immunotherapies. We investigated the utility of circulating tumor cells (CTCs) and circulating white blood cells (WBCs) as a noninvasive method to evaluate PD-L1 status in advanced NSCLC patients. Patients and methods: CTCs and circulating WBCs were enriched from peripheral blood samples (ISET® platform; Rarecells) from 106 NSCLC patients. PD-L1 expression on ISET filters and matched-tumor tissue was evaluated by automated immunostaining (SP142 antibody; Ventana), and quantified in tumor cells and WBCs. Results: CTCs were detected in 80 (75%) patients, with levels ranging from 2 to 256 CTCs/4 ml, and median of 60 CTCs/4 ml. Among 71 evaluable samples with matched-tissue and CTCs, 6 patients (8%) showed ≥1 PD-L1-positive CTCs and 11 patients (15%) showed ≥1% PD-L1-positive tumor cells in tumor tissue with 93% concordance between tissue and CTCs (sensitivity = 55%; specificity = 100%). From 74 samples with matched-tissue and circulating WBCs, 40 patients (54%) showed ≥1% PD-L1-positive immune infiltrates in tumor tissue and 39 patients (53%) showed ≥1% PD-L1 positive in circulating WBCs, with 80% concordance between blood and tissue (sensitivity = 82%; specificity = 79%). We found a trend for worse survival in patients receiving first-line cisplatin-based chemotherapy treatments, whose tumors express PD-L1 in CTCs or immune cells (progression-free and overall survival), similar to the effects of PD-L1 expression in matched-patient tumors. Conclusions: These results demonstrated that PD-L1 status in CTCs and circulating WBCs correlate with PD-L1 status in tumor tissue, revealing the potential of CTCs assessment as a noninvasive real-time biopsy to evaluate PD-L1 expression in patients with advanced-stage NSCLC.
Background: Expression of PD-L1 in tumor cells and tumor-infiltrating immune cells has been associated with improved efficacy to anti-PD-1/PD-L1 inhibitors in patients with advanced-stage non-small-cell lung cancer (NSCLC) and emerged as a potential biomarker for the selection of patients to cancer immunotherapies. We investigated the utility of circulating tumor cells (CTCs) and circulating white blood cells (WBCs) as a noninvasive method to evaluate PD-L1 status in advanced NSCLCpatients. Patients and methods: CTCs and circulating WBCs were enriched from peripheral blood samples (ISET® platform; Rarecells) from 106 NSCLCpatients. PD-L1 expression on ISET filters and matched-tumor tissue was evaluated by automated immunostaining (SP142 antibody; Ventana), and quantified in tumor cells and WBCs. Results: CTCs were detected in 80 (75%) patients, with levels ranging from 2 to 256 CTCs/4 ml, and median of 60 CTCs/4 ml. Among 71 evaluable samples with matched-tissue and CTCs, 6 patients (8%) showed ≥1 PD-L1-positive CTCs and 11 patients (15%) showed ≥1% PD-L1-positive tumor cells in tumor tissue with 93% concordance between tissue and CTCs (sensitivity = 55%; specificity = 100%). From 74 samples with matched-tissue and circulating WBCs, 40 patients (54%) showed ≥1% PD-L1-positive immune infiltrates in tumor tissue and 39 patients (53%) showed ≥1% PD-L1 positive in circulating WBCs, with 80% concordance between blood and tissue (sensitivity = 82%; specificity = 79%). We found a trend for worse survival in patients receiving first-line cisplatin-based chemotherapy treatments, whose tumors express PD-L1 in CTCs or immune cells (progression-free and overall survival), similar to the effects of PD-L1 expression in matched-patienttumors. Conclusions: These results demonstrated that PD-L1 status in CTCs and circulating WBCs correlate with PD-L1 status in tumor tissue, revealing the potential of CTCs assessment as a noninvasive real-time biopsy to evaluate PD-L1 expression in patients with advanced-stage NSCLC.
Authors: Muhammad A Khattak; Anna Reid; James Freeman; Michelle Pereira; Ashleigh McEvoy; Johnny Lo; Markus H Frank; Tarek Meniawy; Ali Didan; Isaac Spencer; Benhur Amanuel; Michael Millward; Melanie Ziman; Elin Gray Journal: Oncologist Date: 2019-12-05
Authors: Elena María Brozos-Vázquez; Roberto Díaz-Peña; Jorge García-González; Luis León-Mateos; Patricia Mondelo-Macía; María Peña-Chilet; Rafael López-López Journal: Cancer Immunol Immunother Date: 2020-10-28 Impact factor: 6.968
Authors: Menno Tamminga; Sanne de Wit; Ed Schuuring; Wim Timens; Leon W M M Terstappen; T Jeroen N Hiltermann; Harry J M Groen Journal: Transl Lung Cancer Res Date: 2019-12