IL1R2 Blockade Alleviates Immunosuppression and Potentiates Anti-PD-1 Efficacy in Triple-Negative Breast Cancer

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	IL1R2 Blockade Alleviates Immunosuppression and Potentiates Anti-PD-1 Efficacy in Triple-Negative Breast Cancer
	Xia, J; Zhang, LX; Peng, XL; Tu, JCL; Li, SQ; He, XY; Li, FK; Qiang, JK; Dong, HA; Deng, QD; Liu, CC; Xu, JH; Zhang, R; Liu, QT; Hu, GH; Liu, C; Jiang, YZ; Shao, ZM; Chen, CS; Liu, SL
	2024
发表期刊	CANCER RESEARCH
ISSN	0008-5472
卷号	84 期号:14 页码:2282-2296
摘要	Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with limited therapeutic options. IL1 receptor type 2 (IL1R2) promotes breast tumor-initiating cell (BTIC) self-renewal and tumor growth in TNBC, indicating that targeting it could improve patient treatment. In this study, we observed that IL1R2 blockade strongly attenuated macrophage recruitment and the polarization of tumor-associated macrophages (TAM) to inhibit BTIC self-renewal and CD8(+) T-cell exhaustion, which resulted in reduced tumor burden and prolonged survival in TNBC mouse models. IL1R2 activation by TAM-derived IL1 beta increased PD-L1 expression by interacting with the transcription factor Yin Yang 1 (YY1) and inducing YY1 ubiquitination and proteasomal degradation in both TAMs and TNBC cells. Loss of YY1 alleviated the transcriptional repression of c-Fos, which is a transcriptional activator of PDL-1. Combined treatment with an IL1R2-neutralizing antibodies and anti-PD-1 led to enhanced antitumor efficacy and reduced TAMs, BTICs, and exhausted CD8+ T cells. These results suggest that IL1R2 blockade might be a strategy to potentiate immune checkpoint blockade efficacy in TNBC to improve patient outcomes. Significance: IL1R2 in both macrophages and breast cancer cells orchestrates an immunosuppressive tumor microenvironment by upregulating PD-L1 expression and can be targeted to enhance the efficacy of anti-PD-1 in triple-negative breast cancer.
收录类别	sci
语种	英语
文献类型	期刊论文
条目标识符	http://ir.kiz.ac.cn/handle/152453/14230
专题	科研部门_肿瘤生物学（陈策实）
推荐引用方式 GB/T 7714	Xia, J,Zhang, LX,Peng, XL,et al. IL1R2 Blockade Alleviates Immunosuppression and Potentiates Anti-PD-1 Efficacy in Triple-Negative Breast Cancer[J]. CANCER RESEARCH,2024,84(14):2282-2296.
APA	Xia, J.,Zhang, LX.,Peng, XL.,Tu, JCL.,Li, SQ.,...&Liu, SL.(2024).IL1R2 Blockade Alleviates Immunosuppression and Potentiates Anti-PD-1 Efficacy in Triple-Negative Breast Cancer.CANCER RESEARCH,84(14),2282-2296.
MLA	Xia, J,et al."IL1R2 Blockade Alleviates Immunosuppression and Potentiates Anti-PD-1 Efficacy in Triple-Negative Breast Cancer".CANCER RESEARCH 84.14(2024):2282-2296.

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