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
  • 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. [email protected].
  • 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. [email protected].
  • # 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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