The authors thank the Core Facility “Medical Genomics” at Tomsk National Research Medical Center (Tomsk NRMC) for providing access to the equipment used in this study.
Author contributions
ESG: Conceptualization, Investigation, Formal analysis, Visualization, Writing—original draft, Writing—review & editing. AYK, EOS, EVK: Investigation, Validation, LAT: Writing—review & editing, Supervision. All authors read and approved the submitted version.
Conflicts of interest
The authors declare that they have no conflicts of interest related to this work.
Ethical approval
The study received approval from the local ethics committee of the Tomsk NRMC Institutional Review Board on August 25, 2020, with approval No. 7.
Consent to participate
Informed consent to participate in the study was obtained from all participants.
Consent to publication
Informed consent to publication was obtained from relevant participants.
Availability of data and materials
The datasets supporting the findings of this study are available from the corresponding author upon reasonable request.
Funding
The authors received no financial support for the research, authorship, and/or publication of this article.
Open Exploration maintains a neutral stance on jurisdictional claims in published institutional affiliations and maps. All opinions expressed in this article are the personal views of the author(s) and do not represent the stance of the editorial team or the publisher.
References
Krystel-Whittemore M, Tan PH, Wen HY. Predictive and prognostic biomarkers in breast tumours.Pathology. 2024;56:186–91. [DOI] [PubMed] [PMC]
Tian Y, Yang Y, He L, Yu X, Zhou H, Wang J. Exploring the tumor microenvironment of breast cancer to develop a prognostic model and predict immunotherapy responses.Sci Rep. 2025;15:12569. [DOI] [PubMed] [PMC]
Liu K, Shi J, Liu J, Zhang Y, Liang J, Xu J, et al. The influence of cell-cell fusion on cancer heterogeneity and its promise for targeted treatments.Cell Oncol (Dordr). 2026;49:22. [DOI] [PubMed] [PMC]
Cozzo AJ, Coleman MF, Hursting SD. You complete me: tumor cell-myeloid cell nuclear fusion as a facilitator of organ-specific metastasis.Front Oncol. 2023;13:1191332. [DOI] [PubMed] [PMC]
Zucker A, Anderson AN, Ekstrom TJ, Fowler KL, Giske NR, Moore AG, et al. Tumor-immune hybrid cell biology: A review of its potential impact in oncology.Cancer Lett. 2026;641:218313. [DOI] [PubMed]
Hass R, von der Ohe J, Dittmar T. Hybrid Formation and Fusion of Cancer Cells In Vitro and In Vivo.Cancers. 2021;13:4496. [DOI] [PubMed] [PMC]
Xiao M, Li X. The impact of the tumor microenvironment on macrophages.Front Immunol. 2025;16:1572764. [DOI] [PubMed] [PMC]
Wei G, Li B, Huang M, Lv M, Liang Z, Zhu C, et al. Polarization of Tumor Cells and Tumor-Associated Macrophages: Molecular Mechanisms and Therapeutic Targets.MedComm. 2025;6:e70372. [DOI] [PubMed] [PMC]
Aguirre LA, Montalbán-Hernández K, Avendaño-Ortiz J, Marín E, Lozano R, Toledano V, et al. Tumor stem cells fuse with monocytes to form highly invasive tumor-hybrid cells.OncoImmunology. 2020;9:1773204. [DOI] [PubMed] [PMC]
Strizova Z, Benesova I, Bartolini R, Novysedlak R, Cecrdlova E, Foley LK, et al. M1/M2 macrophages and their overlaps – myth or reality?Clin Sci (Lond). 2023;137:1067–93. [DOI] [PubMed] [PMC]
Akhter MZ, Sharawat SK, Kumar V, Kochat V, Equbal Z, Ramakrishnan M, et al. Aggressive serous epithelial ovarian cancer is potentially propagated by EpCAM+CD45+ phenotype.Oncogene. 2018;37:2089–103. [DOI] [PubMed]
Lu S, Sun Z, Liu L, Li P, Li B, Li W, et al. Tumor-Derived Exosomes Regulate Apoptosis of CD45+EpCAM+ Cells in Lung Cancer.Front Immunol. 2022;13:903882. [DOI] [PubMed] [PMC]
Mousset CM, Hobo W, Woestenenk R, Preijers F, Dolstra H, van der Waart AB. Comprehensive Phenotyping of T Cells Using Flow Cytometry.Cytometry A. 2019;95:647–54. [DOI] [PubMed]
Loibl S, André F, Bachelot T, Barrios CH, Bergh J, Burstein HJ, et al.; ESMO Guidelines Committee. Electronic address: clinicalguidelines@esmo.org. Early breast cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up.Ann Oncol. 2024;35:159–82. [DOI] [PubMed]
Xu Y, Wang X, Liu L, Wang J, Wu J, Sun C. Role of macrophages in tumor progression and therapy (Review).Int J Oncol. 2022;60:57. [DOI] [PubMed] [PMC]
Bied M, Ho WW, Ginhoux F, Blériot C. Roles of macrophages in tumor development: a spatiotemporal perspective.Cell Mol Immunol. 2023;20:983–92. [DOI] [PubMed] [PMC]
Mukhamedzhanov RK, Grigoryeva ES, Tashyreva LA, Perelmuter VM, Zavyalova MV, Savelieva OE. Assessment of metastatic traits of the cells with hybrid phenotype in breast cancer.Bulletin of RSMU. 2023:4–15. [DOI]
Huang L, Yang Y, Yang F, Liu S, Zhu Z, Lei Z, et al. Functions of EpCAM in physiological processes and diseases (Review).Int J Mol Med. 2018;42:1771–85. [DOI] [PubMed] [PMC]
Wang S, Wang J, Chen Z, Luo J, Guo W, Sun L, et al. Targeting M2-like tumor-associated macrophages is a potential therapeutic approach to overcome antitumor drug resistance.npj Precis Oncol. 2024;8:31. [DOI] [PubMed] [PMC]
Jayasingam SD, Citartan M, Thang TH, Mat Zin AA, Ang KC, Ch’ng ES. Evaluating the Polarization of Tumor-Associated Macrophages Into M1 and M2 Phenotypes in Human Cancer Tissue: Technicalities and Challenges in Routine Clinical Practice.Front Oncol. 2020;9:1512. [DOI] [PubMed] [PMC]
Furgiuele S, Descamps G, Cascarano L, Boucq A, Dubois C, Journe F, et al. Dealing with Macrophage Plasticity to Address Therapeutic Challenges in Head and Neck Cancers.Int J Mol Sci. 2022;23:6385. [DOI] [PubMed] [PMC]
Inic Z, Zegarac M, Inic M, Markovic I, Kozomara Z, Djurisic I, et al. Difference between Luminal A and Luminal B Subtypes According to Ki-67, Tumor Size, and Progesterone Receptor Negativity Providing Prognostic Information.Clin Med Insights: Oncol. 2014;8:107–11. [DOI] [PubMed] [PMC]
Zhang C, Wei S, Dai S, Li X, Wang H, Zhang H, et al. The NR_109/FUBP1/c-Myc axis regulates TAM polarization and remodels the tumor microenvironment to promote cancer development.J ImmunoTher Cancer. 2023;11:e006230. [DOI] [PubMed] [PMC]
Munir MT, Kay MK, Kang MH, Rahman MM, Al-Harrasi A, Choudhury M, et al. Tumor-Associated Macrophages as Multifaceted Regulators of Breast Tumor Growth.Int J Mol Sci. 2021;22:6526. [DOI] [PubMed] [PMC]
Vitale I, Manic G, Coussens LM, Kroemer G, Galluzzi L. Macrophages and Metabolism in the Tumor Microenvironment.Cell Metab. 2019;30:36–50. [DOI] [PubMed]
Fang C, Cheung MY, Chan RC, Poon IK, Lee C, To CC, et al. Prognostic Significance of CD163+ and/or CD206+ Tumor-Associated Macrophages Is Linked to Their Spatial Distribution and Tumor-Infiltrating Lymphocytes in Breast Cancer.Cancers. 2024;16:2147. [DOI] [PubMed] [PMC]
Egeblad M, Ewald AJ, Askautrud HA, Truitt ML, Welm BE, Bainbridge E, et al. Visualizing stromal cell dynamics in different tumor microenvironments by spinning disk confocal microscopy.Dis Model Mech. 2008;1:155–67. [DOI] [PubMed] [PMC]
Huang YK, Wang M, Sun Y, Di Costanzo N, Mitchell C, Achuthan A, et al. Macrophage spatial heterogeneity in gastric cancer defined by multiplex immunohistochemistry.Nat Commun. 2019;10:3928. [DOI] [PubMed] [PMC]