Chordoma cancer stem cell subpopulation characterization may guide targeted immunotherapy approaches to reduce disease recurrence.

Abstract

Introduction:

Cancer stem cells (CSCs), a group of tumor-initiating and tumor-maintaining cells, may be major players in the treatment resistance and recurrence distinctive of chordoma. Characterizing CSCs is crucial to better targeting this subpopulation.

Methods:

Using flow cytometry, six chordoma cell lines were evaluated for CSC composition. In vitro, cell lines were stained for B7H6, HER2, MICA-B, ULBP1, EGFR, and PD-L1 surface markers. Eighteen resected chordomas were stained using a multispectral immunofluorescence (mIF) antibody panel to identify CSCs in vivo. HALO software was used for quantitative CSC density and spatial analysis.

Results:

In vitro, chordoma CSCs express more B7H6, MICA-B, and ULBP1, assessed by percent positivity and mean fluorescence intensity (MFI), as compared to non-CSCs in all cell lines. PD- L1 percent positivity is increased by >20% in CSCs compared to non-CSCs in all cell lines except CH22. In vivo, CSCs comprise 1.39% of chordoma cells and most are PD-L1+ (75.18%). A spatial analysis suggests that chordoma CSCs cluster at an average distance of 71.51 mm (SD 73.40 mm) from stroma.

Discussion:

To our knowledge, this study is the first to identify individual chordoma CSCs and describe their surface phenotypes using in vitro and in vivo methods. PD-L1 is overexpressed on CSCs in chordoma human cell lines and operative tumor samples. Similarly, potential immunotherapeutic targets on CSCs, including B7H6, MICA-B, ULBP1, EGFR, and HER2 are overexpressed across cell lines. Targeting these markers may have a preferential role in combating CSCs, an aggressive subpopulation likely consequential to chordoma's high recurrence rate.

• Authors: Diana C Lopez, Kellsye P Fabian, Michelle R Padget, Yvette L Robbins, Joshua T Kowalczyk, Wiem Lassoued, Danielle M Pastor, Clint T Allen, Gary L Gallia, James L Gulley, James W Hodge, Nyall R London Jr
• Journal: Frontiers in oncology (Front Oncol) Vol. 14 Pg. 1376622 ( 2024) ISSN: 2234-943X [Print] Switzerland
• PMID: 38741774 (Publication Type: Journal Article)
• Copyright: Copyright © 2024 Lopez, Fabian, Padget, Robbins, Kowalczyk, Lassoued, Pastor, Allen, Gallia, Gulley, Hodge and London.