Targeting ANXA1 abrogates Treg-mediated immune suppression in triple-negative breast cancer

Background Regulatory T (Treg) cells play a negative role in anti-tumor immunity against triple-negative breast cancer, so it is of great significance to find the potential therapeutic target of Treg cells.Methods First, Annexin A1 (ANXA1) expression and survival of patients with breast cancer were...

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Main Authors: Bin Li, Peng Zhang, Dan li, Fang Bai, Yipeng Fu, Hongliang Chen, Mingdi Zhang, Qianru Huang, Kejin Wu
Format: Article
Language:English
Published: BMJ Publishing Group 2020-05-01
Series:Journal for ImmunoTherapy of Cancer
Online Access:https://jitc.bmj.com/content/8/1/e000169.full
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author Bin Li
Peng Zhang
Dan li
Fang Bai
Yipeng Fu
Hongliang Chen
Mingdi Zhang
Qianru Huang
Kejin Wu
author_facet Bin Li
Peng Zhang
Dan li
Fang Bai
Yipeng Fu
Hongliang Chen
Mingdi Zhang
Qianru Huang
Kejin Wu
author_sort Bin Li
collection DOAJ
description Background Regulatory T (Treg) cells play a negative role in anti-tumor immunity against triple-negative breast cancer, so it is of great significance to find the potential therapeutic target of Treg cells.Methods First, Annexin A1 (ANXA1) expression and survival of patients with breast cancer were analyzed using TCGA data. Then plasma ANXA1 levels in patients with malignant and benign breast tumors were detected by ELISA. Next, the effect of ANXA1 on Treg cells was studied through suppressive assays, and how ANXA1 regulates the function of Treg cells was detected by RNA sequencing. Finally, the in vivo experiment in balb/c mice was conducted to test whether the ANXA1 blocker Boc1 could shrink tumors and affect the function of Treg cells.Results Our data suggest that ANXA1 expression is associated with lower survival and a higher risk of breast malignancy. Suppressive assays show that ANXA1 can enhance the inhibition function of Treg cells. RNA-Sequencing results indicate that Boc1 could reduce the expression of granzyme A mRNA in Treg cells. Animal experiments have been done to show that Boc1 can reduce tumor size and down regulate Treg cell function.Conclusions ANXA1 can enhance the function of Treg cells and reduce the survival rate of patients with breast cancer. Targeting ANXA1 can reduce Treg cell function and shrink breast tumors.
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institution Kabale University
issn 2051-1426
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publishDate 2020-05-01
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series Journal for ImmunoTherapy of Cancer
spelling doaj-art-6e3eddf223ac423dafab8bbec18efc692024-11-09T12:00:07ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262020-05-018110.1136/jitc-2019-000169Targeting ANXA1 abrogates Treg-mediated immune suppression in triple-negative breast cancerBin Li0Peng Zhang1Dan li2Fang Bai3Yipeng Fu4Hongliang Chen5Mingdi Zhang6Qianru Huang7Kejin Wu8Department of Thoracic Surgery, The Second Affiliated Hospital of Lanzhou University, Lanzhou University, Lanzhou, Gansu, ChinaThe Seventh People’s Hospital of Zhengzhou, Zhengzhou, Henan, ChinaEye Institute and Department of Ophthalmology, Eye & ENT Hospital, Fudan University, Shanghai, People`s Republic of China1 Breast Surgery, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China1 Breast Surgery, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China1 Breast Surgery, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China1 Breast Surgery, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China2 Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai, China1 Breast Surgery, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, ChinaBackground Regulatory T (Treg) cells play a negative role in anti-tumor immunity against triple-negative breast cancer, so it is of great significance to find the potential therapeutic target of Treg cells.Methods First, Annexin A1 (ANXA1) expression and survival of patients with breast cancer were analyzed using TCGA data. Then plasma ANXA1 levels in patients with malignant and benign breast tumors were detected by ELISA. Next, the effect of ANXA1 on Treg cells was studied through suppressive assays, and how ANXA1 regulates the function of Treg cells was detected by RNA sequencing. Finally, the in vivo experiment in balb/c mice was conducted to test whether the ANXA1 blocker Boc1 could shrink tumors and affect the function of Treg cells.Results Our data suggest that ANXA1 expression is associated with lower survival and a higher risk of breast malignancy. Suppressive assays show that ANXA1 can enhance the inhibition function of Treg cells. RNA-Sequencing results indicate that Boc1 could reduce the expression of granzyme A mRNA in Treg cells. Animal experiments have been done to show that Boc1 can reduce tumor size and down regulate Treg cell function.Conclusions ANXA1 can enhance the function of Treg cells and reduce the survival rate of patients with breast cancer. Targeting ANXA1 can reduce Treg cell function and shrink breast tumors.https://jitc.bmj.com/content/8/1/e000169.full
spellingShingle Bin Li
Peng Zhang
Dan li
Fang Bai
Yipeng Fu
Hongliang Chen
Mingdi Zhang
Qianru Huang
Kejin Wu
Targeting ANXA1 abrogates Treg-mediated immune suppression in triple-negative breast cancer
Journal for ImmunoTherapy of Cancer
title Targeting ANXA1 abrogates Treg-mediated immune suppression in triple-negative breast cancer
title_full Targeting ANXA1 abrogates Treg-mediated immune suppression in triple-negative breast cancer
title_fullStr Targeting ANXA1 abrogates Treg-mediated immune suppression in triple-negative breast cancer
title_full_unstemmed Targeting ANXA1 abrogates Treg-mediated immune suppression in triple-negative breast cancer
title_short Targeting ANXA1 abrogates Treg-mediated immune suppression in triple-negative breast cancer
title_sort targeting anxa1 abrogates treg mediated immune suppression in triple negative breast cancer
url https://jitc.bmj.com/content/8/1/e000169.full
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