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Charlotte Rolny's Group

Deciphering underlying mechanisms that regulate pro-tumoral macrophage phenotypes

We focus on dissecting the underlying mechanism that regulate Tumor-associated macrophages (TAMs) immunosuppressive phenotype. Macrophages are sentinel and effector cells with an inherent need to efficiently adapt to changing environmental cues to maintain homeostasis. During tumor growth, macrophages can acquire a spectrum of pro-inflammatory (M1-like) to healing (M2-like) subtypes that change dynamically throughout tumor growth (Figure 1). TAMs initially restrain tumor growth by expressing high levels antigen presenting molecules and pro-inflammatory factors that recruit and activate cytotoxic lymphocytes such as CD8+ T cells. However, with increased malignancy, TAMs acquire an immunosuppressive phenotype, via various mechanisms. TAMs do not only control T cell activation but are also highly interlinked with tumor vasculature l in mammary cancer as well as human  breast cancer (Figure 2).Indeed, we and others have showed that TAMs regulate tumor vascular permeability and leakiness which enable tumor cells to intravasate the vessels and disseminate to distant organs. Hence,  by using multiple strategies that reprograming of pro-tumoral/immunosuppressive TAMs into immunoactivating TAMs, tumor growth and metastatic dissemination can be inhibited by conducting the following projects:

Current projects

  • Selective TAM mRNA regulation during tumor growth.
  • Regulation of angiostatic TAMs that control vessel normalization and metastatic dissemination.
  • Metabolic pathways that regulate TAM phenotypes.
  • Exploiting TAM subtypes for chemotherapy efficacy.
  • Tyrosine kinase signaling pathways that are involved in the microglia- glioma stem cell cross-talk.
  • Mechanism that regulate selective proliferatory control of pro-tumoral TAM subtypes in mammary and human ER+ breast cancer.
Figure 1 and 2

Group members

Charlotte Rolny, Associate Professor, Group leader
Dongmei Tong, Post-doctoral fellow
Sabrina de Souza Ferreira, Post-doctoral fellow
Yangxun Pan, PhD student
Majken Wallerius, affiliated
Margarita Bartish, affiliated

Funding

  • Swedish Research Council (VR)
  • Swedish Cancer Society
  • Cancer Society in Stockholm
  • Karolinska Institutet Funds

Selected publications

STAT3 Activity Promotes Programmed-Death Ligand 1 Expression and Suppresses Immune Responses in Breast Cancer.
Zerdes I, Wallerius M, Sifakis EG, Wallmann T, Betts S, Bartish M, et al
Cancers (Basel) 2019 Oct;11(10):

A Novel ACKR2-Dependent Role of Fibroblast-Derived CXCL14 in Epithelial-to-Mesenchymal Transition and Metastasis of Breast Cancer.
Sjöberg E, Meyrath M, Milde L, Herrera M, Lövrot J, Hägerstrand D, et al
Clin. Cancer Res. 2019 Jun;25(12):3702-3717

Distinct Cancer-Promoting Stromal Gene Expression Depending on Lung Function.
Sandri BJ, Masvidal L, Murie C, Bartish M, Avdulov S, Higgins L, et al
Am. J. Respir. Crit. Care Med. 2019 Aug;200(3):348-358

Microglia Induce PDGFRB Expression in Glioma Cells to Enhance Their Migratory Capacity.
Wallmann T, Zhang XM, Wallerius M, Bolin S, Joly AL, Sobocki C, et al
iScience 2018 Nov;9():71-83

Cripto-1 Plasmid DNA Vaccination Targets Metastasis and Cancer Stem Cells in Murine Mammary Carcinoma.
Witt K, Ligtenberg MA, Conti L, Lanzardo S, Ruiu R, Wallmann T, et al
Cancer Immunol Res 2018 11;6(11):1417-1425

Zoledronic acid inhibits NFAT and IL-2 signaling pathways in regulatory T cells and diminishes their suppressive function in patients with metastatic cancer.
Sarhan D, Leijonhufvud C, Murray S, Witt K, Seitz C, Wallerius M, et al
Oncoimmunology 2017 ;6(8):e1338238

Reprogramming Tumor-Associated Macrophages by Antibody Targeting Inhibits Cancer Progression and Metastasis.
Georgoudaki AM, Prokopec KE, Boura VF, Hellqvist E, Sohn S, Östling J, et al
Cell Rep 2016 05;15(9):2000-11

Guidance Molecule SEMA3A Restricts Tumor Growth by Differentially Regulating the Proliferation of Tumor-Associated Macrophages.
Wallerius M, Wallmann T, Bartish M, Östling J, Mezheyeuski A, Tobin NP, et al
Cancer Res. 2016 06;76(11):3166-78

Brain structure. Cell types in the mouse cortex and hippocampus revealed by single-cell RNA-seq.
Zeisel A, Muñoz-Manchado AB, Codeluppi S, Lönnerberg P, La Manno G, Juréus A, et al
Science 2015 Mar;347(6226):1138-42

HRG inhibits tumor growth and metastasis by inducing macrophage polarization and vessel normalization through downregulation of PlGF.
Rolny C, Mazzone M, Tugues S, Laoui D, Johansson I, Coulon C, et al
Cancer Cell 2011 Jan;19(1):31-44