ORIGINAL RESEARCH article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Integrative analysis of bulk and single-cell transcriptomics identifies factors related to immunosuppressive microenvironment to predict unfavorable prognosis in inflammatory breast cancer
Provisionally accepted
Kexuan Feng1Xiaoduo Li1Xiaoqian Li1Junjie Liu1Rui Zhang1Heyan Chen2Yunpeng Zhang1
Jianjun He1*
Huimin Zhang1*- 1The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
- 2Fujian Medical University Union Hospital, Fuzhou, China
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Inflammatory breast cancer (IBC) is a rare invasive tumor and characterized by the formation of tumor emboli within dermal lymphatic vessels. The tumor microenvironment (TME) is a key factor in IBC aggressiveness, but its heterogeneity and intercellular role remain incompletely understood. Weighted gene coexpression network analysis (WGCNA) was performed to identify immune infiltration-associated genes. We also depicted cellular communication networks and specific ligand-receptor signaling pathways using the single-cell transcriptomics analysis of IBC and non-IBC samples. Finally, we verified the expression of key proteins by immunohistochemistry. Through the intersection of WGCNA module genes and differentially expressed genes between pathological complete response and residual disease samples, GZMB was identified as hub gene which is related to immune infiltration and efficacy of neoadjuvant therapy in IBC. In IBC cohort, patients with high expression of GZMB harbored more immunosuppressive cells thus showed unfavorable prognosis compared with GZMB-low expression group (p<0.05). Subsequent to dimension reduction and clustering, 12 clusters were identified to construct the single-cell atlas between IBC and non-IBC samples. Cellular communication analysis unveiled the heterogeneity of cell communication in IBC. The proportion of immune cells was significantly lower than that of malignant epithelial cells in the cellular composition of IBC. Moreover, it indicated that SPP1 and plasmacytoid dendritic cells were specific in IBC and associated with an immunosuppressive microenvironment in IBC. Immunohistochemical analysis suggested that protein levels of GZMB and SPP1 tended to be higher in the samples from patients with residual disease compared to the patient achieving pathological complete response, though this observation is based on an extremely small sample size. This study identifies GZMB and SPP1 as potential immunosuppressive-related prognostic biomarkers in IBC patients, reveals the key role of plasmacytoid dendritic cells in remodeling of immunosuppressive microenvironment in IBC.
Keywords: Immunosuppressive microenvironment, inflammatory breast cancer, plasmacytoid dendritic cells, prognostic biomarker, Single-cell transcriptomics
Received: 18 Oct 2025; Accepted: 15 Dec 2025.
Copyright: © 2025 Feng, Li, Li, Liu, Zhang, Chen, Zhang, He and Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Jianjun He
Huimin Zhang
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.