2. Academic Validation
  3. Targeting B7-H3 inhibition-induced activation of fatty acid synthesis boosts anti-B7-H3 immunotherapy in triple-negative breast cancer

Targeting B7-H3 inhibition-induced activation of fatty acid synthesis boosts anti-B7-H3 immunotherapy in triple-negative breast cancer

  • J Immunother Cancer. 2025 Apr 12;13(4):e010924. doi: 10.1136/jitc-2024-010924.
Ying Jiang # 1,  Zhiwen Qian # 2,  Cenzhu Wang # 3,  Danping Wu 1,  Lu Liu 1,  Xin Ning 1,  Yilan You 2,  Jie Mei 4,  Xiaoqian Zhao 5,  Yan Zhang 6 2
Affiliations

Affiliations

  • 1 Department of Oncology, Women's Hospital of Jiangnan University, Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu, China.
  • 2 Department of Oncology, Wuxi Maternal and Child Health Hospital, Nanjing Medical University, Nanjing, Jiangsu, China.
  • 3 Department of Oncology, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi People's Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi, Jiangsu, China.
  • 4 The First Clinical Medicine College, Nanjing Medical University, Nanjing, Jiangsu, China meijie1996@njmu.edu.cn snoppyy1980@163.com fuyou2007@126.com.
  • 5 Department of Breast Surgery, Women's Hospital of Jiangnan University, Wuxi, China meijie1996@njmu.edu.cn snoppyy1980@163.com fuyou2007@126.com.
  • 6 Department of Oncology, Women's Hospital of Jiangnan University, Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu, China meijie1996@njmu.edu.cn snoppyy1980@163.com fuyou2007@126.com.
  • # Contributed equally.
PMID: 40221152 DOI: 10.1136/jitc-2024-010924
Abstract

Background: Triple-negative breast Cancer (TNBC) is the most malignant breast Cancer, highlighting the need for effective immunotherapeutic targets. The immune checkpoint molecule B7-H3 has recently gained attention as a promising therapeutic target due to its pivotal role in promoting tumorigenesis and Cancer progression. However, the therapeutic impact of B7-H3 inhibitors (B7-H3i) remains unclear.

Methods: Transcriptomic and metabolomic analyses were conducted to explore the underlying mechanisms of B7-H3 inhibition in TNBC. The therapeutic efficacy of the combined treatment strategy was substantiated through comprehensive phenotypic assays conducted in vitro and validated in vivo using animal models.

Results: B7-H3 blockade induces a "primed for death" stress state in Cancer cells, leading to distinct alterations in metabolic pathways. Specifically, B7-H3 knockdown activated the Akt signaling pathway and upregulated sterol regulatory element-binding protein 1 (SREBP1), which in turn elevated FASN expression. The simultaneous inhibition of both B7-H3 and FASN more effectively attenuated the malignant progression of TNBC.

Conclusions: Our findings propose an "immune attack-metabolic compensation" dynamic model and suggest the feasibility of a dual-targeting strategy that concurrently inhibits both B7-H3 and FASN to enhance therapeutic efficacy in TNBC patients.

Keywords

Breast Cancer; Immune Checkpoint Inhibitor; Immunotherapy.

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