2. Academic Validation
  3. Unveiling the key mechanisms of FOLR2+ macrophage-mediated antitumor immunity in breast cancer using integrated single-cell RNA sequencing and bulk RNA sequencing

Unveiling the key mechanisms of FOLR2+ macrophage-mediated antitumor immunity in breast cancer using integrated single-cell RNA sequencing and bulk RNA sequencing

  • Breast Cancer Res. 2025 Mar 5;27(1):31. doi: 10.1186/s13058-025-01980-4.
Sixuan Wu # 1 2,  Baohong Jiang # 3,  Zhimin Li # 1,  Yuanbin Tang 1,  Lunqi Luo 1,  Wenjie Feng 1,  Yiling Jiang 1,  Yeru Tan 4,  Yuehua Li 5
Affiliations

Affiliations

  • 1 Department of Oncology, the First Affiliated Hospital, Hengyang Medical School, University of South China, No. 69 Chuanshan Road, Hengyang, 421001, Hunan Province, People's Republic of China.
  • 2 Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, 350014, Fujian, People's Republic of China.
  • 3 Department of Pharmacy, the First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan Province, People's Republic of China.
  • 4 Department of Oncology, the First Affiliated Hospital, Hengyang Medical School, University of South China, No. 69 Chuanshan Road, Hengyang, 421001, Hunan Province, People's Republic of China. tanyeru@163.com.
  • 5 Department of Oncology, the First Affiliated Hospital, Hengyang Medical School, University of South China, No. 69 Chuanshan Road, Hengyang, 421001, Hunan Province, People's Republic of China. liyuehua2020@stu.usc.edu.cn.
  • # Contributed equally.
PMID: 40045365 DOI: 10.1186/s13058-025-01980-4
Abstract

Breast Cancer (BRCA) is a common malignant tumor, and its immune microenvironment plays a crucial role in disease progression. In this research, we utilized single-cell RNA Sequencing and bulk RNA Sequencing technologies, combined with in vivo and in vitro experiments, to thoroughly investigate the immunological functions and mechanisms of FOLR2+ macrophages in BRCA. Our findings demonstrate a significant enhancement in the interaction between FOLR2+ macrophages and CD8+ T cells within the tumor tissues of BRCA patients. FOLR2 is closely associated with T cell infiltration in the tumor microenvironment of BRCA patients, particularly with CD8+ T cells. By secreting CXCL9 and engaging with CXCR3, FOLR2+ macrophages can activate the functionality of CD8+ T cells, thereby promoting Cancer cell Apoptosis. Further animal experiments confirm that FOLR2+ macrophages activate CD8+ T cells through the CXCL9-CXCR3 axis, exhibiting an antitumor immunity effect in BRCA. FOLR2+ macrophages play a crucial role in antitumor immunity in BRCA through the CXCL9-CXCR3 axis.

Keywords

BRCA; CD8+ T cells; CXCL9-CXCR3 axis; FOLR2+ macrophages; Immune microenvironment; Single-cell RNA sequencing.

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