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Exp. Mol. Med., Nov 07 2025, | https://doi.org/10.1038/s12276-025-01571-5
Single-cell transcriptomics of the myeloid milieu reveals an angiogenic niche in triple-negative breast cancer
Yechan Choi 1 †, Minkyu Shim 1 †, Suhn Hyung Kim 1, Duk Ki Kim 1 2, Juhee Jeong 1 2, Jinyoung Byeon 3 4 5, Giyong Jang 6 7, Ji-Yeon Kim 8, Paul Robson 9, Charles Lee 9 *, Han-Byoel Lee 3 4 5 *, Keehoon Jung 1 2 *
1Department of Anatomy and Cell Biology, Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea.
2Institute of Allergy and Clinical Immunology, Seoul National University Medical Research Center, Seoul, Republic of Korea.
3Department of Surgery, Seoul National University College of Medicine, Seoul, Republic of Korea.
4Cancer Research Institute, Seoul National University, Seoul, Republic of Korea.
5Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea.
6Genomic Medicine Institute, Medical Research Center, Seoul National University, Seoul, Republic of Korea.
7Ewha Biomedical Research Institute, Ewha Womans University Medical Center, Seoul, Republic of Korea.
8Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
9The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA.
2Institute of Allergy and Clinical Immunology, Seoul National University Medical Research Center, Seoul, Republic of Korea.
3Department of Surgery, Seoul National University College of Medicine, Seoul, Republic of Korea.
4Cancer Research Institute, Seoul National University, Seoul, Republic of Korea.
5Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea.
6Genomic Medicine Institute, Medical Research Center, Seoul National University, Seoul, Republic of Korea.
7Ewha Biomedical Research Institute, Ewha Womans University Medical Center, Seoul, Republic of Korea.
8Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
9The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA.
†These authors contributed equally
*Corresponding authors: correspondence to Charles Lee, Han-Byoel Lee or Keehoon Jung
Abstract
Intratumoral myeloid cells are highly heterogeneous in terms of development and function and are pivotal for forming and regulating the tumor microenvironment. However, the myeloid milieu in triple-negative breast cancer (TNBC) remains poorly understood. Here, to elucidate this myeloid milieu, we integrated in-house and public single-cell RNA sequencing data. We detected diverse neutrophil and mononuclear-phagocyte subtypes and delineated their developmental trajectories and functions. Of particular interest were the VEGFAhi neutrophil and SPP1hi macrophage subtypes, which displayed protumoral functions, including angiogenesis. Spatial transcriptomics revealed that they colocalized with epithelial cancer cells and APLNhi endothelial tip cells in a hypoxic region forming an angiogenic niche. Moreover, patients with SPP1hi macrophage-enriched TNBC showed poor prognosis, which worsened in patients who also displayed abundant VEGFAhi neutrophils. These subtypes were also conserved in multiple murine TNBC models. This comprehensive analysis of the myeloid population in TNBC thus reveals a previously undercharacterized interaction between VEGFAhi neutrophils and SPP1hi macrophages, elucidating their contributions in the formation of an angiogenic niche.
논문정보
- Research article
- 2025년 11월 (BRIC 등록일 2025-11-12)
- 국내(교신)+국외 연구진
- 생명과학 > 면역학
관련 보도자료
‘치료제 없는 암’ 삼중음성유방암, 면역세포의 공간적 비밀에서 실마리 찾았다
서울대학교 의과대학 정기훈 교수 연구팀은 서울대학교병원 이한별 교수 연구팀과의 공동연구를 통해 유방암의 아형 중 예후가 특히 나쁜 삼중음성유방암(triple negative breast cancer, TNBC) 내 골수성 면역세포들을 단일세포 전사체 연구 기법을 활용하여 연구하였다. 이를 통해 혈관 신생 과정(angiogenesis)에 관여하는 세포들이 모여 있는 국소 환경(niche)을 발견하였으며, 이를 보유하고 있는 환자들의 경우 예후가 특히 부정적인 것을 확인하였다. 이번 연구 결과는 기존 연구에서 등한시 되었던 면역세포들의 공간적 배치가 중요하다는 사실을 보여주는 동시에 새로운 치료 표적을 제안함으로써 향후 삼중음성유방암의 치료 전략 수립에 크게 기여할 것으로 기대된다.
- Bio통신원
- 2025. 11. 18
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