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Journal of Experimental & Clinical Cancer Research

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Open Access 01-12-2024 | Research

Analysis of the effect of CCR7 on the microenvironment of mouse oral squamous cell carcinoma by single-cell RNA sequencing technology

Authors: Zengxu Wang, Keith L. Kirkwood, Yao Wang, Weidong Du, Shanfeng Lin, Wanhang Zhou, Cong Yan, Jiaxing Gao, Zhenning Li, Changfu Sun, Fayu Liu

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2024

Abstract

Background

Studies have shown that CCR7, an important inflammatory factor, can promote the proliferation and metastasis of oral squamous cell carcinoma (OSCC), but its role in the tumor microenvironment (TME) remains unclear. This paper explores the role of CCR7 in the TME of OSCC.

Methods

In this work, we constructed CCR7 gene knockout mice and OSCC mouse models. Single-cell RNA sequencing (scRNA-seq) and bioinformatics were used to analyze the differences in the OSCC microenvironment between three CCR7 gene knockout mice (KO) and three wild-type mice (WT). Immunohistochemistry, immunofluorescence staining, and flow cytometry were used to analyze the expression of key genes in significantly different cell types between the KO and WT groups. An in vitro experiment was used to verify the effect of CCR7 on M2 macrophage polarization.

Results

In the mouse OSCC models, the tumor growth rate in the KO group was significantly lower than that in the WT group. Eight main cell types (including tumor cells, fibroblasts, macrophages, granulocytes, T cells, endothelial cells, monocytes, and B cells) were identified by Seurat analysis. The scRNA-seq results showed that the proportion of tumor cells was lower, but the proportion of inflammatory cells was significantly higher in the KO group than in the WT group. CellPhoneDB analysis results indicated a strong interaction relationship between tumor cells and macrophages, T cells, fibroblasts, and endothelial cells. Functional enrichment results indicated that the expression level of the Dusp1 gene in the KO group was generally higher than that in the WT group in various cell types. Macrophage subclustering results indicated that the proportion of M2 macrophages in the KO group was lower than that in the WT group. In vitro experimental results showed that CCR7 can promote M2 macrophage polarization, thus promoting the proliferation, invasion and migration of OSCC cells.

Conclusions

CCR7 gene knockout can significantly inhibit the growth of mouse oral squamous cell carcinoma by promoting the polarization of M2 macrophages.

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Li Z, Zhang L, Liu F, Li P, He J, Kirkwood C, Sohn J, Chan J, Magner W, Kirkwood KJOo. MKP-1 is required to limit myeloid-cell mediated oral squamous cell carcinoma progression and regional extension. Oral Oncol. 2021;120:105401.PubMedCrossRef

Title: Analysis of the effect of CCR7 on the microenvironment of mouse oral squamous cell carcinoma by single-cell RNA sequencing technology
Authors: Zengxu Wang
Keith L. Kirkwood
Yao Wang
Weidong Du
Shanfeng Lin
Wanhang Zhou
Cong Yan
Jiaxing Gao
Zhenning Li
Changfu Sun
Fayu Liu
Publication date: 01-12-2024
Publisher: BioMed Central
Published in: Journal of Experimental & Clinical Cancer Research / Issue 1/2024
Electronic ISSN: 1756-9966
DOI: https://doi.org/10.1186/s13046-024-03013-y

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