Single-Cell Transcriptome Analysis Reveals Changes of Tumor Immune Microenvironment in Oral Squamous Cell Carcinoma After Chemotherapy

Hao Song; Chao Lou; Jie Ma; Qiyu Gong; Zhuowei Tian; Yuanhe You; Guoxin Ren; Wei Guo; Yanan Wang; Kunyan He; Meng Xiao

doi:10.3389/fcell.2022.914120

Single-Cell Transcriptome Analysis Reveals Changes of Tumor Immune Microenvironment in Oral Squamous Cell Carcinoma After Chemotherapy

Front Cell Dev Biol. 2022 Jun 17:10:914120. doi: 10.3389/fcell.2022.914120. eCollection 2022.

Authors

Hao Song^{1

2}, Chao Lou^{1

2}, Jie Ma³, Qiyu Gong⁴, Zhuowei Tian^{1

2}, Yuanhe You^{1

2}, Guoxin Ren^{1

2}, Wei Guo^{1

2}, Yanan Wang^{1

2}, Kunyan He⁵, Meng Xiao^{1

2}

Affiliations

¹ Department of Oral Maxillofacial-Head and Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
² Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, National Clinical Research Center of Stomatology, Shanghai, China.
³ Department of Implant Dentistry, Shanghai Xuhui District Dental Center, Shanghai, China.
⁴ Shanghai Institute of Immunology, Faculty of Basic Medicine, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
⁵ Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, China.

Abstract

Induction chemotherapy in oral squamous cell carcinoma is a controversial issue in clinical practice. To investigate the evolution of cancer cells and tumor microenvironment (TME) response to chemotherapy in oral squamous cell carcinoma, single-cell transcriptome analysis was performed in a post-chemotherapy squamous cell carcinoma located in oral cavity. The main cell types were identified based on gene expression patterns determined using dimensionality reduction and unsupervised cell clustering. Non-negative matrix factorization clustering of the gene expression of Cancer-associated fibroblasts (CAFs) and macrophages was performed. Kyoto Encyclopedia of Genes and Genomes pathway analyses and gene set enrichment analysis were performed to explore significant functional pathways. CellPhoneDB and NicheNet were used to detect the intercellular communication between cell types. CAFs were divided into "inflammatory CAFs," "antigen-presenting CAFs" and "myofibroblastic CAFs." Three classic subgroups of tumor-associated macrophages (TAMs) were detected, namely C1Q (+), FCN1 (+) and SPP1(+) TAMs. The inflammatory cytokine expression is elevated, and several molecular pathways, such as PI3K/Akt/mTORC1, TNF-α via NFκB, TGF-β, IL-6/JAK2/STAT3 and CXCL12/CXCR4 axis associated with epithelial-mesenchymal transition were enriched in TME. Also, CD74-MIF/COPA/APP interactions were expressed in TME of oral squamous cell carcinoma after chemotherapy. The results revealed the characteristics of TME in post-chemotherapy oral squamous cell carcinoma at single-cell transcriptome level, providing new insights and clues for further investigation.

Keywords: cancer-associated fibroblasts (CAFs); introduction chemotherapy; oral squamous cell carcinoma (OSCC); single-cell sequencing (scRNA-seq); tumor microenvironment.