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CD24hiCD27+ 转移性淋巴结内的Bregs促进乳腺癌多药性耐药性

Huanhuan Huang^1,2,3,4, Yao Yao^1,2,3, Lesang Shen^1,2,3

¹Department of Breast Surgery, Second Affiliated Hospital, Zhejiang University, Hangzhou, Zhejiang, P.R. China.

Clinical cancer research : an official journal of the American Association for Cancer Research

|October 13, 2023

概括

乳腺癌淋巴结中的调控性B细胞 (Bregs) 促进耐药性. 通过化疗阻断PD-L1可以改善瘤缓解,提供一种新的化疗免疫治疗策略.

科学领域:

免疫学免疫学免疫学
在瘤学瘤学.
细胞生物学细胞生物学

背景情况:

轴淋巴结是乳腺癌中的主要转移部位.
转移性淋巴结 (mLNs) 中的瘤微环境和免疫细胞相互作用的理解很少.
调控性B细胞 (Bregs) 参与免疫调节.

研究的目的:

为了研究CD24hiCD27+ Bregs在乳腺癌患者的mLNs中的作用.
探索Bregs对乳腺癌细胞耐药性的影响.
评估针对布雷格-瘤细胞相互作用的治疗策略.

主要方法:

分析乳腺癌患者的mLN样本后的新辅助疗法 (NAT).
多色免疫光染色用于CD24hiCD27+ Bregs的空间分析.
实验室耐药性测定和mLNs的小鼠模型.
评估PD-L1阻塞和化疗免疫疗法.

主要成果:

在NAT后的mLN中,激活的CD24hiCD27+ Bregs和残留瘤细胞之间存在密切的空间相关性.
CD24hiCD27+ Bregs通过IL6和TNFα分泌增强乳腺癌细胞中的多药性耐药性和干状特征.
通过CD40L和PD-L1信号在乳腺癌细胞和Bregs之间建立了一个积极的反循环.
PD-L1阻塞降低了Breg诱导的耐药性,而抗PD-L1与化疗相结合改善了mLNs中的瘤回归.

结论:

CD24hiCD27+ Bregs在促进乳腺癌在mLN中的耐药性方面发挥着至关重要的作用.
针对Bregs和乳腺癌细胞之间的相互作用提供了一个有希望的治疗途径.
涉及PD-L1阻断的组合化疗免疫疗法代表了乳腺癌患者有淋巴结转移的改善策略.

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