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Published on: July 20, 2019
Targeting ANXA1 abrogates Treg-mediated immune suppression in triple-negative breast cancer
Fang Bai1, Peng Zhang1, Yipeng Fu1
1Breast Surgery, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China.
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.
Insights
Regulatory T (Treg) cells suppress anti-tumor immunity in triple-negative breast cancer. Targeting Annexin A1 (ANXA1) with Boc1 reduces Treg cell function and tumor size, offering a potential therapeutic strategy.
Area of Science:
- Immunology
- Oncology
- Molecular Biology
Background:
- Regulatory T (Treg) cells impede anti-tumor immunity in triple-negative breast cancer.
- Identifying therapeutic targets for Treg cells is crucial for improving cancer treatment.
Purpose of the Study:
- To investigate the role of Annexin A1 (ANXA1) in breast cancer progression and its effect on Treg cells.
- To evaluate the therapeutic potential of targeting ANXA1 in breast cancer.
Main Methods:
- Analysis of TCGA data for ANXA1 expression and patient survival.
- ELISA to measure plasma ANXA1 levels in breast tumor patients.
- In vitro suppressive assays and RNA sequencing to study ANXA1's effect on Treg cells.
- In vivo experiments using Boc1, an ANXA1 blocker, in mice models.
Main Results:
- ANXA1 expression correlates with decreased survival and increased breast malignancy risk.
- ANXA1 enhances the suppressive function of Treg cells.
- Boc1 treatment reduced tumor size and Treg cell function in vivo, decreasing granzyme A mRNA expression in Treg cells.
Conclusions:
- ANXA1 promotes Treg cell function and reduces breast cancer patient survival.
- Targeting ANXA1 with Boc1 demonstrates potential for reducing Treg cell activity and shrinking breast tumors.
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