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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
neuroscience
Control of tumor-associated macrophages and T cells in glioblastoma via AHR and CD39
Nature Neuroscience, Volume 22, No. 5, Year 2019
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Description
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. © 2019, The Author(s), under exclusive licence to Springer Nature America, Inc.
Authors & Co-Authors
Rothhammer, Veit
United States, Boston
Brigham and Women's Hospital
Mascanfroni, Iván Darío
United States, Boston
Brigham and Women's Hospital
Kenison, Jessica E.
United States, Boston
Brigham and Women's Hospital
Sherr, David H.
United States, Boston
School of Public Health
Farez, Mauricio Franco
Argentina, Buenos Aires
Instituto de Investigaciones Neurologicas Raul Carrera
Prat, Alexandre
Canada, Montreal
University of Montreal
Antel, Jack P.
Canada, Montreal
Université Mcgill
Reardon, David A.
United States, Boston
Dana-farber Cancer Institute
Zhang, Hailei
United States, Cambridge
Massachusetts Institute of Technology
Robson, Simon Christopher
United States, Boston
Beth Israel Deaconess Medical Center
Getz, Gad A.
United States, Cambridge
Massachusetts Institute of Technology
Quintana, Francisco J.
United States, Boston
Brigham and Women's Hospital
United States, Cambridge
Massachusetts Institute of Technology
Statistics
Citations: 278
Authors: 12
Affiliations: 8
Identifiers
Doi:
10.1038/s41593-019-0370-y
ISSN:
10976256
Research Areas
Cancer