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S100A9-CXCL12 activation in BRCA1-mutant breast cancer promotes an immunosuppressive microenvironment associated with resistance to immunotherapy
Li, Jianjie1,2; Shu, Xiaodong1,2; Xu, Jun1,2; Su, Sek Man1,2; Chan, Un In1,2; Mo, Lihua1,2; Liu, Jianlin1,2; Zhang, Xin1,2; Adhav, Ragini1,2; Chen, Qiang1,2; Wang, Yuqing1,2; An, Tingting1,2; Zhang, Xu1,2; Lyu, Xueying1,2; Li, Xiaoling1,2; Lei, Josh Haipeng1,2; Miao, Kai1,2,3; Sun, Heng1,2,3; Xing, Fuqiang1,2; Zhang, Aiping1,2; Deng, Chuxia1,2,3; Xu, Xiaoling1,2,3
2022-03-18
Source PublicationNature Communications
ISSN2041-1723
Volume13Issue:1
Other Abstract

Immune checkpoint blockade (ICB) is a powerful approach for cancer therapy although good responses are only observed in a fraction of cancer patients. Breast cancers caused by deficiency of breast cancer-associated gene 1 (BRCA1) do not have an improved response to the treatment. To investigate this, here we analyze BRCA1 mutant mammary tissues and tumors derived from both BRCA1 mutant mouse models and human xenograft models to identify intrinsic determinants governing tumor progression and ICB responses. We show that BRCA1 deficiency activates S100A9-CXCL12 signaling for cancer progression and triggers the expansion and accumulation of myeloid-derived suppressor cells (MDSCs), creating a tumor-permissive microenvironment and rendering cancers insensitive to ICB. These oncogenic actions can be effectively suppressed by the combinatory treatment of inhibitors for S100A9-CXCL12 signaling with αPD-1 antibody. This study provides a selective strategy for effective immunotherapy in patients with elevated S100A9 and/or CXCL12 protein levels.

DOI10.1038/s41467-022-29151-5
URLView the original
Indexed BySCIE
Language英語English
WOS Research AreaScience & Technology - Other Topics
WOS SubjectMultidisciplinary Sciences
WOS IDWOS:000770716000016
Scopus ID2-s2.0-85126712934
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Cited Times [WOS]:3   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionFaculty of Health Sciences
DEPARTMENT OF BIOMEDICAL SCIENCES
Corresponding AuthorDeng, Chuxia; Xu, Xiaoling
Affiliation1.Cancer Centre, Faculty of Health Sciences, University of Macau, Macao
2.Centre for Precision Medicine Research and Training, Faculty of Health Sciences, University of Macau, Macao
3.MOE Frontier Science Centre for Precision Oncology, University of Macau, Macao
First Author AffilicationCancer Centre;  Faculty of Health Sciences
Corresponding Author AffilicationCancer Centre;  Faculty of Health Sciences;  University of Macau
Recommended Citation
GB/T 7714
Li, Jianjie,Shu, Xiaodong,Xu, Jun,et al. S100A9-CXCL12 activation in BRCA1-mutant breast cancer promotes an immunosuppressive microenvironment associated with resistance to immunotherapy[J]. Nature Communications,2022,13(1).
APA Li, Jianjie.,Shu, Xiaodong.,Xu, Jun.,Su, Sek Man.,Chan, Un In.,Mo, Lihua.,Liu, Jianlin.,Zhang, Xin.,Adhav, Ragini.,Chen, Qiang.,Wang, Yuqing.,An, Tingting.,Zhang, Xu.,Lyu, Xueying.,Li, Xiaoling.,Lei, Josh Haipeng.,Miao, Kai.,Sun, Heng.,Xing, Fuqiang.,...&Xu, Xiaoling.(2022).S100A9-CXCL12 activation in BRCA1-mutant breast cancer promotes an immunosuppressive microenvironment associated with resistance to immunotherapy.Nature Communications,13(1).
MLA Li, Jianjie,et al."S100A9-CXCL12 activation in BRCA1-mutant breast cancer promotes an immunosuppressive microenvironment associated with resistance to immunotherapy".Nature Communications 13.1(2022).
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