Details

Autor(en) / Beteiligte

• Wang, Junfeng
• Wang, Quanyi
• Guan, Yinan
• Sun, Yulu
• Wang, Xiaozhi
• Lively, Kaylie
• Wang, Yuzhen
• Luo, Ming
• Kim, Julian A
• Murphy, E. Angela
• Yao, Yongzhong
• Cai, Guoshuai
• Fan, Daping

Titel

Breast cancer cell–derived microRNA-155 suppresses tumor progression via enhancing immune cell recruitment and antitumor function

Ist Teil von

• The Journal of clinical investigation, 2022-10, Vol.132 (19), p.1-16

Ort / Verlag

Ann Arbor: American Society for Clinical Investigation

Erscheinungsjahr

2022

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• Evidence suggests that increased microRNA-155 (miR-155) expression in immune cells enhances antitumor immune responses. However, given the reported association of miR-155 with tumorigenesis in various cancers, a debate is provoked on whether miR-155 is oncogenic or tumor suppressive. We aimed to interrogate the impact of tumor miR-155 expression, particularly that of cancer cell-derived miR-155, on antitumor immunity in breast cancer. We performed bioinformatics analysis of human breast cancer databases, murine experiments, and human specimen examination. We revealed that higher tumor miR-155 levels correlate with a favorable antitumor immune profile and better patient outcomes. Murine experiments demonstrated that miR-155 overexpression in breast cancer cells enhanced T cell influx, delayed tumor growth, and sensitized the tumors to immune checkpoint blockade (ICB) therapy. Mechanistically, miR-155 overexpression in breast cancer cells upregulated their CXCL9/10/11 production, which was mediated by SOCS1 inhibition and increased phosphorylated STAT1 (p-STAT1)/p-STAT3 ratios. We further found that serum miR-155 levels in breast cancer patients correlated with tumor miR155 levels and tumor immune status. Our findings suggest that high serum and tumor miR-155 levels may be a favorable prognostic marker for breast cancer patients and that therapeutic elevation of miR-155 in breast tumors may improve the efficacy of ICB therapy via remodeling the antitumor immune landscape.