Control of tumor-associated macrophages and T cells in glioblastoma via AHR and CD39

Takenaka MC, Gabriely G, Rothhammer V, Mascanfroni ID, Wheeler MA, Chao CC, Gutierrez-Vazquez C, Kenison J, Tjon EC, Barroso A, Vandeventer T, De Lima KA, Rothweiler S, Mayo L, Ghannam S, Zandee S, Healy L, Sherr D, Farez MF, Pratt A, Antel J, Reardon DA, Zhang H, Robson SC, Getz G, Weiner HL, Quintana FJ (2019)

Publication Type: Journal article

Publication year: 2019

Journal

Nature Neuroscience Nature Publishing Group

Book Volume: 22

Pages Range: 729-740

Journal Issue: 5

DOI: 10.1038/s41593-019-0370-y

Abstract

Tumor-associated macrophages (TAMs) play an important role in the immune response to cancer, but the mechanisms by which the tumor microenvironment controls TAMs and T cell immunity are not completely understood. Here we report that kynurenine produced by glioblastoma cells activates aryl hydrocarbon receptor (AHR) in TAMs to modulate their function and T cell immunity. AHR promotes CCR2 expression, driving TAM recruitment in response to CCL2. AHR also drives the expression of KLF4 and suppresses NF-κB activation in TAMs. Finally, AHR drives the expression of the ectonucleotidase CD39 in TAMs, which promotes CD8+ T cell dysfunction by producing adenosine in cooperation with CD73. In humans, the expression of AHR and CD39 was highest in grade 4 glioma, and high AHR expression was associated with poor prognosis. In summary, AHR and CD39 expressed in TAMs participate in the regulation of the immune response in glioblastoma and constitute potential targets for immunotherapy.

Authors with CRIS profile

Veit Rothhammer

Involved external institutions

Harvard University US United States (USA) (US) Brigham and Women's Hospital (BWH) US United States (USA) (US) Université de Montréal CA Canada (CA) Boston University US United States (USA) (US) Eli and Edythe L. Broad Institute of MIT and Harvard US United States (USA) (US) McGill University CA Canada (CA) Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia (FLENI) AR Argentina (AR)

How to cite

APA:

Takenaka, M.C., Gabriely, G., Rothhammer, V., Mascanfroni, I.D., Wheeler, M.A., Chao, C.-C.,... Quintana, F.J. (2019). Control of tumor-associated macrophages and T cells in glioblastoma via AHR and CD39. Nature Neuroscience, 22(5), 729-740. https://dx.doi.org/10.1038/s41593-019-0370-y

MLA:

Takenaka, Maisa C., et al. "Control of tumor-associated macrophages and T cells in glioblastoma via AHR and CD39." Nature Neuroscience 22.5 (2019): 729-740.

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