Low infiltration of tumor-associated macrophages in high c-Myb-expressing breast tumors

• Published in: Scientific reports 2019-08, Vol.9 (1), p.11634-9, Article 11634
• Main Authors: Volodko, Nataliya, Gutor, Taras, Petronchak, Orest, Huley, Roman, Dúcka, Monika, Šmarda, Jan, Borsig, Lubor, Beneš, Petr, Knopfová, Lucia
• Format: Article
• Language: English
• Subjects: 38/39; 38/61; 38/91; 631/67/1347; 631/67/1857; 631/67/327; 82/51; Adult; Aged; Aged, 80 and over; Antigens, CD - metabolism; Antigens, Differentiation, Myelomonocytic - metabolism; Breast - pathology; Breast cancer; Breast Neoplasms - genetics; Breast Neoplasms - immunology; Breast Neoplasms - mortality; Breast Neoplasms - pathology; c-Myb protein; CD163 antigen; Cell Proliferation; Cohort Studies; Datasets as Topic; Female; Gene Expression Profiling; Gene Expression Regulation, Neoplastic - immunology; Humanities and Social Sciences; Humans; Kaplan-Meier Estimate; Macrophages; Macrophages - immunology; Macrophages - metabolism; Metastases; Middle Aged; multidisciplinary; Prognosis; Proto-Oncogene Proteins c-myb - metabolism; Receptors, Cell Surface - metabolism; Science; Science (multidisciplinary); Stroma; Transformed cells; Tumor cells; Tumor Microenvironment - genetics; Tumor Microenvironment - immunology; Tumorigenesis; Tumors
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-019-48051-1

Tumor-associated macrophages (TAMs) are prominent components of tumor stroma that promotes tumorigenesis. Many soluble factors participate in the deleterious cross-talk between TAMs and transformed cells; however mechanisms how tumors orchestrate their production remain relatively unexplored. c-Myb is a transcription factor recently described as a negative regulator of a specific immune signature involved in breast cancer (BC) metastasis. Here we studied whether c-Myb expression is associated with an increased presence of TAMs in human breast tumors. Tumors with high frequency of c-Myb-positive cells have lower density of CD68-positive macrophages. The negative association is reflected by inverse correlation between MYB and CD68/CD163 markers at the mRNA levels in evaluated cohorts of BC patients from public databases, which was found also within the molecular subtypes. In addition, we identified potential MYB -regulated TAMs recruiting factors that in combination with MYB and CD163 provided a valuable clinical multigene predictor for BC relapse. We propose that identified transcription program running in tumor cells with high MYB expression and preventing macrophage accumulation may open new venues towards TAMs targeting and BC therapy.