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

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-alpha via NF kappa B, TGF-beta, 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.

Automated summary

The study investigated the tumor microenvironment and tumor cell evolution in oral squamous cell carcinoma after chemotherapy using single-cell transcriptome analysis. The results identified different types of cancer-associated fibroblasts and tumor-associated macrophages in the tumor microenvironment, and enriched molecular pathways associated with epithelial-mesenchymal transition. Additionally, the study found the expression of CD74-MIF/COPA/APP interactions in the tumor microenvironment after chemotherapy. These findings provide new insights for further research.