Optimization of the Enrichment of Circulating Tumor Cells for Downstream Phenotypic Analysis in Patients with Non-Small Cell Lung Cancer Treated with Anti-PD-1 Immunotherapy

Autor: Maria Papadaki, Christina Vasilopoulou, Sofia Agelaki, Konstantinos Rounis, Afroditi I Sotiriou, Panormitis G Tsoulfas, Despoina Aggouraki, Christina A Apostolopoulou, Dimitrios Mavroudis, Maria Filika
Rok vydání: 2020
Předmět:
PD-L1
0301 basic medicine
Cancer Research
medicine.medical_treatment
circulating tumor cells
NSCLC
lcsh:RC254-282
Article
IDO
immune checkpoint inhibitors
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Circulating tumor cell
Antigen
ISET
medicine
Parsortix
ICIs
Liquid biopsy
Lung cancer
neoplasms
non-small cell lung cancer
immune evasion
liquid biopsy
biology
business.industry
indoleamine-2
3-dioxygenase
Epithelial cell adhesion molecule
Immunotherapy
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
medicine.disease
respiratory tract diseases
3. Good health
programmed cell death-1 ligand
030104 developmental biology
Oncology
chemistry
030220 oncology & carcinogenesis
Cancer research
biology.protein
immunotherapy
CTCs
business
Progressive disease
Zdroj: Cancers
Volume 12
Issue 6
Cancers, Vol 12, Iss 1556, p 1556 (2020)
ISSN: 2072-6694
DOI: 10.3390/cancers12061556
Popis: The current study aimed at the optimization of circulating tumor cell (CTC) enrichment for downstream protein expression analyses in non-small cell lung cancer (NSCLC) to serve as a tool for the investigation of immune checkpoints in real time. Different enrichment approaches&mdash
ficoll density, erythrolysis, their combination with magnetic separation, ISET, and Parsortix&mdash
were compared in spiking experiments using the A549, H1975, and SKMES-1 NSCLC cell lines. The most efficient methods were tested in patients (n = 15) receiving immunotherapy targeting programmed cell death-1 (PD-1). Samples were immunofluorescently stained for a) cytokeratins (CK)/epithelial cell adhesion molecule (EpCAM)/leukocyte common antigen (CD45), and b) CK/programmed cell death ligand-1 (PD-L1)/ indoleamine-2,3-dioxygenase (IDO). Ficoll, ISET, and Parsortix presented the highest yields and compatibility with phenotypic analysis
however, at the patient level, they provided discordant CTC positivity (13%, 33%, and 60% of patients, respectively) and enriched for distinct CTC populations. IDO and PD-L1 were expressed in 44% and 33% and co-expressed in 19% of CTCs. CTC detection was associated with progressive disease (PD) (p = 0.006), reduced progression-free survival PFS (p = 0.007), and increased risk of relapse (hazard ratio
HR: 10.733
p = 0.026). IDO-positive CTCs were associated with shorter PFS (p = 0.039) and overall survival OS (p = 0.021) and increased risk of death (HR: 5.462
p = 0.039). The current study indicates that CTC analysis according to distinct immune checkpoints is feasible and may provide valuable biomarkers to monitor NSCLC patients treated with anti-PD-1 agents.
Databáze: OpenAIRE
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