Schwann Cell-Mediated M2-Like Macrophage Polarization in Rhabdomyosarcoma

Guanying Feng; Yibo Guo; Mingtao Chen; Yu Zhang; Zheqi Liu; Chen Sun; Xin Hu; Chengzhong Lin; Yu Liu; Yue Wu; Hao Wu; Xi Yang; Yang Wang; Jinhai Ye; Jiannan Liu; Xu Wang; Tong Ji; Chenping Zhang

doi:10.1111/odi.15214

Schwann Cell-Mediated M2-Like Macrophage Polarization in Rhabdomyosarcoma

Oral Dis. 2024 Dec 5. doi: 10.1111/odi.15214. Online ahead of print.

Authors

Guanying Feng^{1

2

3

4

5

6}, Yibo Guo⁷, Mingtao Chen⁷, Yu Zhang⁷, Zheqi Liu⁷, Chen Sun^{1

2

3

4

5

6}, Xin Hu^{1

2

3

4

5

6}, Chengzhong Lin⁷, Yu Liu^{1

2

3

4

5

6}, Yue Wu^{1

2

3

4

5

6}, Hao Wu^{1

2

3

4

5

6}, Xi Yang^{1

2

3

4

5

6}, Yang Wang⁷, Jinhai Ye⁷, Jiannan Liu^{1

2

3

4

5

6}, Xu Wang^{1

2

3

4

5

6}, Tong Ji⁷, Chenping Zhang^{1

2

3

4

5

6}

Affiliations

¹ Department of Oral Maxillofacial-Head Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
² College of Stomatology, Shanghai Jiao Tong University, Shanghai, China.
³ National Center for Stomatology, Shanghai, China.
⁴ National Clinical Research Center for Oral Diseases, Shanghai, China.
⁵ Shanghai Key Laboratory of Stomatology, Shanghai, China.
⁶ Shanghai Research Institute of Stomatology, Shanghai, China.
⁷ Department of Oral and Maxillofacial Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.

PMID: 39639424
DOI: 10.1111/odi.15214

Abstract

Objective: To investigate the cellular components and immunological characteristics of the head and neck rhabdomyosarcoma (RMS) microenvironment.

Methods: We conducted single-cell transcriptomics to analyze the cellular components of the RMS microenvironment. CellChat was utilized for analyzing intercellular interactions. The cancer genome atlas database was used for validation. CIBERSORT was applied for immune infiltration profiling. Functional enrichment analyses were performed using the Kyoto Encyclopedia of Genes and Genomes. Gene set scores were calculated using single-sample gene set enrichment analysis. Subcutaneous allograft models and bulk RNA sequencing were used for validation. Flow cytometry and immunohistochemistry were used to identify M2-like macrophages.

Results: Our findings revealed an extremely low presence of neutrophils in RMS samples compared with normal sample. RMS sample with high Schwann cell infiltration exhibited an increase in M2-like macrophage infiltration. Receptor-ligand pairs, specifically MIF-CD74 and PTN-SDC3, were identified between Schwann cells and M2-like macrophages. In the RMS sample characterized by significant Schwann cell infiltration, M2-like macrophages demonstrate robust expression of axon guidance factors and are enriched in the axon guidance pathway.

Conclusions: Our study provides valuable insights into the microenvironment and immunological characteristics of RMS, offering crucial information for further research and potential therapeutic strategies.

Keywords: M2‐like macrophage polarization; Schwann cell; axon guidance; head and neck rhabdomyosarcoma; single‐cell transcriptome analysis; soft tissue sarcoma.