{"doi":"10.3389/fonc.2024.1376622","title":"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.","journal":"Frontiers in Oncology","year":2024,"id":467885,"datarank":0.20794415416798362,"base_score":1.3862943611198906,"endowment":1.3862943611198906,"self_citation_contribution":0.20794415416798362,"citation_network_contribution":0.0,"self_endowment_contribution":0.20794415416798362,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.962,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":322335,"name":"Kellsye P. Fabian","orcid":"0000-0002-0273-5647","position":1,"is_corresponding":false},{"id":242494,"name":"Michelle R. Padget","orcid":"0000-0003-4922-1042","position":2,"is_corresponding":false},{"id":322330,"name":"Yvette Robbins","orcid":"0000-0003-0940-3941","position":3,"is_corresponding":false},{"id":401695,"name":"Joshua T. Kowalczyk","orcid":"0000-0002-2212-7809","position":4,"is_corresponding":false},{"id":890302,"name":"Wiem Lassoued","orcid":"0009-0004-5742-6982","position":5,"is_corresponding":false},{"id":530619,"name":"Danielle M. Pastor","orcid":"0000-0003-2732-960X","position":6,"is_corresponding":false},{"id":260382,"name":"Clint Allen","orcid":"0000-0001-6586-5804","position":7,"is_corresponding":false},{"id":459882,"name":"Gary L. Gallia","orcid":"0000-0001-6438-7329","position":8,"is_corresponding":false},{"id":239942,"name":"James L. Gulley","orcid":"0000-0002-6569-2912","position":9,"is_corresponding":false},{"id":242498,"name":"James W. Hodge","orcid":"0000-0001-5282-3154","position":10,"is_corresponding":false},{"id":610842,"name":"Nyall R. London","orcid":"0000-0002-2902-4407","position":11,"is_corresponding":false},{"id":733326,"name":"Diana C. Lopez","orcid":null,"position":0,"is_corresponding":true}],"reference_count":57,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:05:15.025255Z","pmid":"38741774","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}