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Single-Cell Profiling Reveals Heterogeneity of Primary and Lymph Node Metastatic Tumors and Immune Cell Populations and Discovers Important Prognostic Significance of CCDC43 in Oral Squamous Cell Carcinoma

Although substantial progress has been made in biological research and clinical treatment in recent years, the clinical prognosis of oral squamous cell carcinoma (OSCC) is still not satisfactory. Tumor immune microenvironment (TIME) is a potential target, which plays an essential role in the respons...

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Autores principales: Wang, Zhenyu, Zhang, Hongbo, Zhai, Yanan, Li, Fengtong, Shi, Xueying, Ying, Muying
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8986980/
https://www.ncbi.nlm.nih.gov/pubmed/35401551
http://dx.doi.org/10.3389/fimmu.2022.843322
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author Wang, Zhenyu
Zhang, Hongbo
Zhai, Yanan
Li, Fengtong
Shi, Xueying
Ying, Muying
author_facet Wang, Zhenyu
Zhang, Hongbo
Zhai, Yanan
Li, Fengtong
Shi, Xueying
Ying, Muying
author_sort Wang, Zhenyu
collection PubMed
description Although substantial progress has been made in biological research and clinical treatment in recent years, the clinical prognosis of oral squamous cell carcinoma (OSCC) is still not satisfactory. Tumor immune microenvironment (TIME) is a potential target, which plays an essential role in the response of anti-tumor immunity and immunotherapy. In this study, we used scRNA-seq data, revealing the heterogeneity of TIME between metastatic and primary site. We found that in the metastatic site, the content of cytotoxic T cells and classical activated macrophages (M1 macrophages) increases significantly, while alternately activated macrophages (M2 macrophages) and inflammatory cancer-associated fibroblasts (iCAFs) decrease, which may be due to the increased immunogenicity of OSCC cells in the metastatic site and the changes in some signal pathways. We also found that iCAFs may recruit alternately activated macrophages (M2 macrophages) by secreting CXCL12. Then, we described a regulatory network for communication between various TIME cells centered on OSCC cells, which can help to clarify the possible mechanism of lymph node metastasis in OSCC cells. By performing pseudotime trajectory analysis, we found that the expression CCDC43 is upregulated in more advanced OSCC cells and is an independent prognostic factor for poor living conditions. Other than this, the high expression of CCDC43 may impair the antitumor immunity of the human body and promote the metastasis of OSCC cells. Our research provides a profound insight into the immunological study of OSCC and an essential resource for future drug discovery.
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spelling pubmed-89869802022-04-08 Single-Cell Profiling Reveals Heterogeneity of Primary and Lymph Node Metastatic Tumors and Immune Cell Populations and Discovers Important Prognostic Significance of CCDC43 in Oral Squamous Cell Carcinoma Wang, Zhenyu Zhang, Hongbo Zhai, Yanan Li, Fengtong Shi, Xueying Ying, Muying Front Immunol Immunology Although substantial progress has been made in biological research and clinical treatment in recent years, the clinical prognosis of oral squamous cell carcinoma (OSCC) is still not satisfactory. Tumor immune microenvironment (TIME) is a potential target, which plays an essential role in the response of anti-tumor immunity and immunotherapy. In this study, we used scRNA-seq data, revealing the heterogeneity of TIME between metastatic and primary site. We found that in the metastatic site, the content of cytotoxic T cells and classical activated macrophages (M1 macrophages) increases significantly, while alternately activated macrophages (M2 macrophages) and inflammatory cancer-associated fibroblasts (iCAFs) decrease, which may be due to the increased immunogenicity of OSCC cells in the metastatic site and the changes in some signal pathways. We also found that iCAFs may recruit alternately activated macrophages (M2 macrophages) by secreting CXCL12. Then, we described a regulatory network for communication between various TIME cells centered on OSCC cells, which can help to clarify the possible mechanism of lymph node metastasis in OSCC cells. By performing pseudotime trajectory analysis, we found that the expression CCDC43 is upregulated in more advanced OSCC cells and is an independent prognostic factor for poor living conditions. Other than this, the high expression of CCDC43 may impair the antitumor immunity of the human body and promote the metastasis of OSCC cells. Our research provides a profound insight into the immunological study of OSCC and an essential resource for future drug discovery. Frontiers Media S.A. 2022-03-24 /pmc/articles/PMC8986980/ /pubmed/35401551 http://dx.doi.org/10.3389/fimmu.2022.843322 Text en Copyright © 2022 Wang, Zhang, Zhai, Li, Shi and Ying https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Wang, Zhenyu
Zhang, Hongbo
Zhai, Yanan
Li, Fengtong
Shi, Xueying
Ying, Muying
Single-Cell Profiling Reveals Heterogeneity of Primary and Lymph Node Metastatic Tumors and Immune Cell Populations and Discovers Important Prognostic Significance of CCDC43 in Oral Squamous Cell Carcinoma
title Single-Cell Profiling Reveals Heterogeneity of Primary and Lymph Node Metastatic Tumors and Immune Cell Populations and Discovers Important Prognostic Significance of CCDC43 in Oral Squamous Cell Carcinoma
title_full Single-Cell Profiling Reveals Heterogeneity of Primary and Lymph Node Metastatic Tumors and Immune Cell Populations and Discovers Important Prognostic Significance of CCDC43 in Oral Squamous Cell Carcinoma
title_fullStr Single-Cell Profiling Reveals Heterogeneity of Primary and Lymph Node Metastatic Tumors and Immune Cell Populations and Discovers Important Prognostic Significance of CCDC43 in Oral Squamous Cell Carcinoma
title_full_unstemmed Single-Cell Profiling Reveals Heterogeneity of Primary and Lymph Node Metastatic Tumors and Immune Cell Populations and Discovers Important Prognostic Significance of CCDC43 in Oral Squamous Cell Carcinoma
title_short Single-Cell Profiling Reveals Heterogeneity of Primary and Lymph Node Metastatic Tumors and Immune Cell Populations and Discovers Important Prognostic Significance of CCDC43 in Oral Squamous Cell Carcinoma
title_sort single-cell profiling reveals heterogeneity of primary and lymph node metastatic tumors and immune cell populations and discovers important prognostic significance of ccdc43 in oral squamous cell carcinoma
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8986980/
https://www.ncbi.nlm.nih.gov/pubmed/35401551
http://dx.doi.org/10.3389/fimmu.2022.843322
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