Dataset Information

First evidence of AXL expression on circulating tumor cells in metastatic breast cancer patients: A proof-of-concept study.

ABSTRACT:

Background

For several years, the AXL tyrosine kinase receptor, a member of the Tyro3-Axl-Mer (TAM) family, has been considered a new strategic target in oncology. AXL overexpression is common in solid tumors and is associated with poor prognosis. In this context, the detection of a subset of circulating tumor cells (CTCs) that express AXL (AXL⁺ CTCs) could be clinically relevant.

Methods

Immunostaining was performed to assess AXL expression in human breast cancer cell lines. The optimal conditions were established using flow cytometry. Spiking experiments were carried out to optimize the parameters of the CellSearch^® system detection test. CTC enumeration and AXL expression were evaluated in patients with metastatic breast cancer (mBC) before treatment initiation.

Results

An innovative AXL⁺ CTC detection assay to be used with the CellSearch^® system was developed. In a prospective longitudinal clinical trial, blood samples from 60 patients with untreated mBC were analyzed to detect AXL⁺ CTCs with this new assay. CTCs were detected in 35/60 patients (58.3%) and AXL⁺ CTCs were identified in 7 of these 35 patients (11.7% of all patients).

Conclusion

This newly established AXL⁺ CTC assay is a promising tool that can be used for liquid biopsy in future clinical trials to stratify and monitor patients with cancer receiving anti-AXL therapies.

SUBMITTER: Bardol T

PROVIDER: S-EPMC10807582 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature

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Publications

First evidence of AXL expression on circulating tumor cells in metastatic breast cancer patients: A proof-of-concept study.

Bardol Thomas T Eslami-S Zahra Z Masmoudi Doryan D Alexandre Marie M Duboys de Labarre Marie M Bobrie Angélique A D'Hondt Véronique V Guiu Séverine S Kurma Keerthi K Cayrefourcq Laure L Jacot William W Alix-Panabières Catherine C

Cancer medicine 20231222 1

<h4>Background</h4>For several years, the AXL tyrosine kinase receptor, a member of the Tyro3-Axl-Mer (TAM) family, has been considered a new strategic target in oncology. AXL overexpression is common in solid tumors and is associated with poor prognosis. In this context, the detection of a subset of circulating tumor cells (CTCs) that express AXL (AXL<sup>+</sup> CTCs) could be clinically relevant.<h4>Methods</h4>Immunostaining was performed to assess AXL expression in human breast cancer cell ...[more]

PMID: 38132919

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Project description:BackgroundImmune checkpoint inhibition is effective in several cancers. Expression of programmed death-ligand 1 (PD-L1) on circulating tumor or immune effector cells could provide insights into selection of patients for immune checkpoint inhibition.MethodsWhole blood was collected at serial timepoints from metastatic breast cancer patients and healthy donors for circulating tumor cell (CTC) and platelet PD-L1 analysis with a phycoerythrin-labeled anti-human PD-L1 monoclonal antibody (Biolegend clone 29E.2A3) using the CellSearch® assay. CTC PD-L1 was considered positive if detected on at least 1% of the cells; platelet PD-L1 was considered positive if ≥100 platelets per CellSearch frame expressed PD-L1.ResultsA total of 207 specimens from 124 metastatic breast cancer patients were collected. 52/124 (42%) samples at timepoint-1 (at or close to time of progressive disease) had ≥5 CTC/7.5ml whole blood. Of those, 21 (40%) had positive CTC PD-L1. In addition, platelet PD-L1 expression was observed in 35/124 (28%) at timepoint-1. Platelet PD-L1 was not detected in more than 70 specimens from 12 healthy donors. Platelet PD-L1 was associated with ≥5 CTC/7.5ml whole blood (p = 0.0002), less likely in patients with higher red blood cell counts (OR = 0.72, p<0.001) and a history of smoking tobacco (OR = 0.76, p<0.001). Platelet PD-L1 staining was not associated with tumor marker status, recent procedures or treatments, platelet-affecting drugs, or CTC PD-L1 expression.ConclusionPD-L1 expression was found in metastatic breast cancer patients on both CTC and platelets in an independent fashion. Inter-patient platelet PD-L1 expression was highly heterogeneous suggesting that it is a biological event associated with cancer in some but not all patients. Taken together, our data suggest that CTC and platelet PD-L1 expression could play a role in predicting which patients should receive immune checkpoint inhibition and as a pharmacodynamics biomarker during treatment.

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Dataset Information

First evidence of AXL expression on circulating tumor cells in metastatic breast cancer patients: A proof-of-concept study.

Background

Methods

Results

Conclusion

Publications

First evidence of AXL expression on circulating tumor cells in metastatic breast cancer patients: A proof-of-concept study.

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