IL-6 mediated CD206⁺ARG-1⁺ tumor associated macrophage polarization induces Treg infiltration in non-responder luminal A breast cancer.

IF 3.5 4区生物学 Q1 Biochemistry, Genetics and Molecular Biology

FEBS Letters Pub Date : 2025-02-04 DOI:10.1002/1873-3468.70000

Ananya Das, Sraddhya Roy, Aparajita Bairagi, Neyaz Alam, Nabanita Chatterjee

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Abstract

Drug non-responsiveness is the major reason for the poor prognosis of hormonal receptor-positive breast cancer (ER⁺/PR⁺ BCa), particularly the luminal A subtype. However, the underlying mechanism of drug non-responsiveness remains unknown. Flow cytometry and t-SNE analysis followed by ELISA validation of responder and non-responder unveiled lower secretion of IFN-γ, IL-12, and higher levels of IL-6 and TGF-β in CD4⁺ T cells (P < 0.001), CD8⁺ T cells (P < 0.001), FOXP3⁺ Tregs (P < 0.001) and CD206⁺ TAMs (P < 0.001) in non-responders. Treatment of isolated CD206⁺ TAMs with recombinant IL-6 upregulated the expression of ARG-1 (arginase-1) and subsequent increase of TGF-β⁺ Tregs (P < 0.001) and IL-6⁺ Tregs (P < 0.001) in luminal A BCa. Our findings showed IL-6 mediated ARG-1⁺CD206⁺ TAMs polarization induced FOXP3⁺ Tregs infiltration in TME of non-responder in luminal A BCa.

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药物无应答是激素受体阳性乳腺癌（ER+/PR+ BCa），尤其是管腔 A 亚型预后不良的主要原因。然而，药物无应答的内在机制仍然未知。通过流式细胞术和 t-SNE 分析以及酶联免疫吸附试验（ELISA）对应答者和非应答者进行验证，发现 IFN-γ、IL-12 的分泌较低，而 IL-6 和 TT-1 的分泌较高、P + T细胞（P + Tregs）（P + TAMs）（P + TAMs与重组IL-6可上调ARG-1（精氨酸酶-1）的表达，随后增加TGF-β+ Tregs（P + Tregs）（P +CD206+ TAMs极化诱导FOXP3+ Tregs浸润管腔A型BCa非应答者的TME）。

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来源期刊

FEBS Letters 生物-生化与分子生物学

CiteScore

7.00

自引率

2.90%

发文量

303

审稿时长

1.0 months

期刊介绍： FEBS Letters is one of the world''s leading journals in molecular biology and is renowned both for its quality of content and speed of production. Bringing together the most important developments in the molecular biosciences, FEBS Letters provides an international forum for Minireviews, Research Letters and Hypotheses that merit urgent publication.