Identification of tumor-associated macrophage subsets that are associated with breast cancer prognosis

  • Background: Breast cancer is the leading cause of cancer-related deaths in women, demanding new treatment options. With the advent of immune checkpoint blockade, immunotherapy emerged as a treatment option. In addition to lymphocytes, tumor-associated macrophages exert a significant, albeit controversial, impact on tumor development. Pro-inflammatory macrophages are thought to hinder, whereas anti-inflammatory macrophages promote tumor growth. However, molecular markers to identify prognostic macrophage populations remain elusive. Methods: We isolated two macrophage subsets, from 48 primary human breast tumors, distinguished by the expression of CD206. Their transcriptomes were analyzed via RNA-Seq, and potential prognostic macrophage markers were validated by PhenOptics in tissue microarrays of patients with invasive breast cancer. Results: Normal human breast tissue contained mainly CD206+ macrophages, while increased relative amounts of CD206− macrophages were observed in tumors. The presence of CD206+ macrophages correlated with a pronounced lymphocyte infiltrate and subsets of CD206+ macrophages, expressing SERPINH1 and collagen 1, or MORC4, were unexpectedly associated with improved survival of breast cancer patients. In contrast, MHCIIhi CD206− macrophages were linked with a poor survival prognosis. Conclusion: Our data highlight the heterogeneity of tumor-infiltrating macrophages and suggest the use of multiple phenotypic markers to predict the impact of macrophage subpopulations on cancer prognosis. We identified novel macrophage markers that correlate with the survival of patients with invasive mammary carcinoma.
Author:Elisabeth Strack, P. Alexander Rolfe, Annika Fink, Katrin Bankov, Tobias Schmid, Christine Solbach, Rajkumar SavaiORCiDGND, Weixiao Sha, Leon Pradel, Sylvia HartmannGND, Bernhard BrüneORCiD, Andreas WeigertORCiDGND
Parent Title (English):Clinical and translational medicine
Place of publication:Hoboken, NJ
Document Type:Article
Date of Publication (online):2020/12/06
Date of first Publication:2020/12/06
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2022/03/22
Tag:breast cancer; flow cytometry; macrophage; transcriptome; tumor microenvironment
Issue:8, art. e239
Page Number:17
First Page:1
Last Page:17
This work was supported by Deutsche Krebshilfe (70114051), Deutsche Forschungsgemeinschaft (FOR 2438, TP8; SFB 1039, TP B04 and B06, GRK 2336, TP1 and 6), Wilhelm-Sander Foundation (2019.082.01), the LOEWE Center Frankfurt Cancer Institute (FCI) funded by the Hessen State Ministry for Higher Education, Research and the Arts (III L 5 - 519/03/03.001 - [0015]), and the German Cancer Consortium (DKTK).
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung 4.0