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Journal Article Ppublish

PubMed: 39854870 DOI: 10.1016/j.oraloncology.2025.107181

CD271 cancer stem cells regulate macrophage polarization in head and neck squamous cell carcinoma.

Oral Oncol 162:107181

Authors: Lifan Chen, Ruihua Fang, Zhimou Cai, Bixue Huang, Jinhong Zhang, Yun Li, Yi Chen, Zhenglin Xu, Wenbin Lei, Minjuan Zhang

Affiliations

  • Department of Otolaryngology, The First Affiliated Hospital of Sun Yat-Sen University, PR China.
  • Department of Otolaryngology, The First Affiliated Hospital of Sun Yat-Sen University, PR China.
  • Department of Otolaryngology, The First Affiliated Hospital of Sun Yat-Sen University, PR China.

Abstract

PURPOSE

Cancer stem cells (CSCs) are considered key drivers of progression in head and neck squamous cell carcinoma (HNSCC). Our single-cell RNA sequencing (scRNA-seq) analysis revealed predominant expression of CD271 in CSCs, however, its role as a CSC marker in HNSCC requires further elucidation. We investigated the stemness characteristics of CD271 HNSCC cells and their interactions with the tumor immune microenvironment.

METHODS

scRNA-seq data from hypopharyngeal squamous cell carcinoma (HPSCC) tissues were analyzed to identify expression profile of CSCs. Overall survival was compared between CD271 and CD271 patients based on immunostaining of HPSCC samples. The stemness of CD271 HNSCC cells was evaluated via an in vivo limiting dilution assay. In a C57BL/6 mice model, the percentage of immune cells and macrophage subtypes were analyzed by flow cytometry. The role of CD271 in macrophage polarization was further examined by in vitro coculture of CD271 cells with CD14 monocytes. Gene expressions were analyzed by qPCR.

RESULTS

CD271 is predominantly expressed in CSCs identified by scRNA-seq analysis. CD271 enhances HNSCC cell proliferation and is negatively correlated with patient prognosis in HPSCC. CD271 knockdown suppressed HNSCC tumor growth and regulated macrophage polarization within the TME. CD271 cells exhibited stemness features and enhanced tumor growth in vivo.

CONCLUSIONS

CD271 HNSCC cells exhibit CSC characteristics and regulate macrophage polarization. Targeting CD271 may improve the immunosuppressive TME to inhibit tumor growth. Combining CD271-targeting agents with other therapies presents a promising strategy that may enhance therapeutic efficacy and prognosis in HNSCC.

MeSH

Cells, Growth, Microscopy, Electron, Scanning Transmission, Carcinoma, Squamous Cell, Macrophages, Neoplasms, Stem Cells, Squamous Cell Carcinoma Of Head And Neck, Therapeutics, Prognosis

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