Spi-B Promotes the Recruitment of Tumor-Associated Macrophages via Enhancing CCL4 Expression in Lung Cancer

Tumor immune escape plays a critical role in malignant tumor progression and leads to the failure of anticancer immunotherapy. Spi-B, a lymphocyte lineage-specific Ets transcription factor, participates in mesenchymal invasion and favors metastasis in human lung cancer. However, the mechanism throug...

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Main Authors: Qiumin Huang, Junrong Liu, Shuainan Wu, Xuexi Zhang, Zengtuan Xiao, Zhe Liu, Wei Du
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-06-01
Series:Frontiers in Oncology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fonc.2021.659131/full
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author Qiumin Huang
Junrong Liu
Shuainan Wu
Xuexi Zhang
Zengtuan Xiao
Zhe Liu
Zhe Liu
Zhe Liu
Wei Du
Wei Du
author_facet Qiumin Huang
Junrong Liu
Shuainan Wu
Xuexi Zhang
Zengtuan Xiao
Zhe Liu
Zhe Liu
Zhe Liu
Wei Du
Wei Du
author_sort Qiumin Huang
collection DOAJ
description Tumor immune escape plays a critical role in malignant tumor progression and leads to the failure of anticancer immunotherapy. Spi-B, a lymphocyte lineage-specific Ets transcription factor, participates in mesenchymal invasion and favors metastasis in human lung cancer. However, the mechanism through which Spi-B regulates the tumor immune environment has not been elucidated. In this study, we demonstrated that Spi-B enhanced the infiltration of tumor-associated macrophages (TAMs) in the tumor microenvironment using subcutaneous mouse models and clinical samples of human lung cancer. Spi-B overexpression increased the expression of TAM polarization- and recruitment-related genes, including CCL4. Moreover, deleting CCL4 inhibited the ability of Spi-B promoting macrophage infiltration. These data suggest that Spi-B promotes the recruitment of TAMs to the tumor microenvironment via upregulating CCL4 expression, which contributes to the progression of lung cancer.
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spelling doaj.art-0617f7ee539d45c89a74b4c0ee693b972022-12-21T18:26:31ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2021-06-011110.3389/fonc.2021.659131659131Spi-B Promotes the Recruitment of Tumor-Associated Macrophages via Enhancing CCL4 Expression in Lung CancerQiumin Huang0Junrong Liu1Shuainan Wu2Xuexi Zhang3Zengtuan Xiao4Zhe Liu5Zhe Liu6Zhe Liu7Wei Du8Wei Du9Department of Immunology, Biochemistry and Molecular Biology, 2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, Tianjin Key Laboratory of Medical Epigenetics, Tianjin Medical University, Tianjin, ChinaDepartment of Immunology, Biochemistry and Molecular Biology, 2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, Tianjin Key Laboratory of Medical Epigenetics, Tianjin Medical University, Tianjin, ChinaDepartment of Immunology, Biochemistry and Molecular Biology, 2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, Tianjin Key Laboratory of Medical Epigenetics, Tianjin Medical University, Tianjin, ChinaDepartment of Immunology, Biochemistry and Molecular Biology, 2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, Tianjin Key Laboratory of Medical Epigenetics, Tianjin Medical University, Tianjin, ChinaDepartment of Lung Cancer Center, Tianjin Medical University Cancer Institute and Hospital, Tianjin, ChinaDepartment of Immunology, Biochemistry and Molecular Biology, 2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, Tianjin Key Laboratory of Medical Epigenetics, Tianjin Medical University, Tianjin, ChinaKey Laboratory of Immune Microenvironment and Disease of the Ministry of Education, Tianjin Medical University, Tianjin, ChinaTianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Tianjin, ChinaDepartment of Immunology, Biochemistry and Molecular Biology, 2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, Tianjin Key Laboratory of Medical Epigenetics, Tianjin Medical University, Tianjin, ChinaKey Laboratory of Immune Microenvironment and Disease of the Ministry of Education, Tianjin Medical University, Tianjin, ChinaTumor immune escape plays a critical role in malignant tumor progression and leads to the failure of anticancer immunotherapy. Spi-B, a lymphocyte lineage-specific Ets transcription factor, participates in mesenchymal invasion and favors metastasis in human lung cancer. However, the mechanism through which Spi-B regulates the tumor immune environment has not been elucidated. In this study, we demonstrated that Spi-B enhanced the infiltration of tumor-associated macrophages (TAMs) in the tumor microenvironment using subcutaneous mouse models and clinical samples of human lung cancer. Spi-B overexpression increased the expression of TAM polarization- and recruitment-related genes, including CCL4. Moreover, deleting CCL4 inhibited the ability of Spi-B promoting macrophage infiltration. These data suggest that Spi-B promotes the recruitment of TAMs to the tumor microenvironment via upregulating CCL4 expression, which contributes to the progression of lung cancer.https://www.frontiersin.org/articles/10.3389/fonc.2021.659131/fulltumor-associated macrophageslung cancerCCL4CD163Spi-B
spellingShingle Qiumin Huang
Junrong Liu
Shuainan Wu
Xuexi Zhang
Zengtuan Xiao
Zhe Liu
Zhe Liu
Zhe Liu
Wei Du
Wei Du
Spi-B Promotes the Recruitment of Tumor-Associated Macrophages via Enhancing CCL4 Expression in Lung Cancer
Frontiers in Oncology
tumor-associated macrophages
lung cancer
CCL4
CD163
Spi-B
title Spi-B Promotes the Recruitment of Tumor-Associated Macrophages via Enhancing CCL4 Expression in Lung Cancer
title_full Spi-B Promotes the Recruitment of Tumor-Associated Macrophages via Enhancing CCL4 Expression in Lung Cancer
title_fullStr Spi-B Promotes the Recruitment of Tumor-Associated Macrophages via Enhancing CCL4 Expression in Lung Cancer
title_full_unstemmed Spi-B Promotes the Recruitment of Tumor-Associated Macrophages via Enhancing CCL4 Expression in Lung Cancer
title_short Spi-B Promotes the Recruitment of Tumor-Associated Macrophages via Enhancing CCL4 Expression in Lung Cancer
title_sort spi b promotes the recruitment of tumor associated macrophages via enhancing ccl4 expression in lung cancer
topic tumor-associated macrophages
lung cancer
CCL4
CD163
Spi-B
url https://www.frontiersin.org/articles/10.3389/fonc.2021.659131/full
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