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Peer-reviewedCC BY 4.0PLOS One

Uncovering the immune microenvironmental atlas of breast cancer molecular subtypes based on single-cell transcriptomics

  • Shihua Lin1
  • Yangxinyue Zheng2
  • Zushun Chen3
  • Menoudji Djetoyom Patrice
  • Li Wang
  • Xia Li
  • Yunpeng Zhang
  • Xingda Zhang
  1. 1College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China
  2. 2School of Intelligent Medicine and Technology, Big Data Research Center, Hainan Medical University, Haikou, China
  3. 3Department of Breast Surgery, Harbin Medical University Cancer Hospital, Harbin, China
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Abstract

Breast cancer progression is closely linked to immune cells within the tumor microenvironment (TME), but the immune landscape differences across HER2-positive (HER2+), triple-negative (TNBC), and ER-positive (ER+) subtypes have yet to be systematically characterized. In this study, we characterized immune landscape differences across HER2-positive (HER2+), triple-negative (TNBC), and ER-positive (ER+) breast cancers using single-cell RNA sequencing data, focusing on T cells, macrophages, and B cells. Our analysis revealed that cytotoxic CD8 + T cells were more abundant in TNBC but showed signs of dysfunction. Macrophage subsets, including an NDUFB8 + population, exhibited divergent functional orientations across subtypes. B cells in TNBC exhibited functional alterations, characterized by a decreased proportion of plasmablasts and an increased proportion of memory B cells. Single-cell regulatory network inference and clustering (SCENIC) analysis predicted a set of subtype-specific candidate transcription factors (TFs), including E2F8 across all subtypes and ATF7 in HER2 + tumors, whose activity correlated with clinical outcomes. Finally, mapping multicellular communication networks revealed both conserved and subtype-specific signaling pathways. Together, these results present a detailed transcriptional landscape of immune heterogeneity in breast cancer and contribute novel insights that may inform the design of subtype-specific immunotherapies.

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Cite

BibTeXRIS
BibTeX
@article{lin2026uncovering,
  title = {{Uncovering the immune microenvironmental atlas of breast cancer molecular subtypes based on single-cell transcriptomics}},
  author = {Shihua Lin and Yangxinyue Zheng and Zushun Chen and Menoudji Djetoyom Patrice and Li Wang and Xia Li and Yunpeng Zhang and Xingda Zhang},
  journal = {PLOS One},
  year = {2026},
  month = nov,
  doi = {10.1371/journal.pone.0361987},
  url = {https://doi.org/10.1371/journal.pone.0361987},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Uncovering the immune microenvironmental atlas of breast cancer molecular subtypes based on single-cell transcriptomics
AU  - Shihua Lin
AU  - Yangxinyue Zheng
AU  - Zushun Chen
AU  - Menoudji Djetoyom Patrice
AU  - Li Wang
AU  - Xia Li
AU  - Yunpeng Zhang
AU  - Xingda Zhang
PY  - 2026
DA  - 2026/11/06
JO  - PLOS One
DO  - 10.1371/journal.pone.0361987
UR  - https://doi.org/10.1371/journal.pone.0361987
AB  - Breast cancer progression is closely linked to immune cells within the tumor microenvironment (TME), but the immune landscape differences across HER2-positive (HER2+), triple-negative (TNBC), and ER-positive (ER+) subtypes have yet to be systematically characterized. In this study, we characterized immune landscape differences across HER2-positive (HER2+), triple-negative (TNBC), and ER-positive (ER+) breast cancers using single-cell RNA sequencing data, focusing on T cells, macrophages, and B cells. Our analysis revealed that cytotoxic CD8 + T cells were more abundant in TNBC but showed signs of dysfunction. Macrophage subsets, including an NDUFB8 + population, exhibited divergent functional orientations across subtypes. B cells in TNBC exhibited functional alterations, characterized by a decreased proportion of plasmablasts and an increased proportion of memory B cells. Single-cell regulatory network inference and clustering (SCENIC) analysis predicted a set of subtype-specific candidate transcription factors (TFs), including E2F8 across all subtypes and ATF7 in HER2 + tumors, whose activity correlated with clinical outcomes. Finally, mapping multicellular communication networks revealed both conserved and subtype-specific signaling pathways. Together, these results present a detailed transcriptional landscape of immune heterogeneity in breast cancer and contribute novel insights that may inform the design of subtype-specific immunotherapies.
SN  - 1932-6203
ER  -