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 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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