| Literature DB >> 30962630 |
Maisa C Takenaka1, Galina Gabriely1, Veit Rothhammer1, Ivan D Mascanfroni1, Michael A Wheeler1, Chun-Cheih Chao1, Cristina Gutiérrez-Vázquez1, Jessica Kenison1, Emily C Tjon1, Andreia Barroso1, Tyler Vandeventer1, Kalil Alves de Lima1, Sonja Rothweiler2, Lior Mayo1, Soufiene Ghannam3, Stephanie Zandee3, Luke Healy4, David Sherr5, Mauricio F Farez6,7, Alexandre Prat3, Jack Antel4, David A Reardon8, Hailei Zhang9, Simon C Robson2, Gad Getz9, Howard L Weiner1, Francisco J Quintana10,11.
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.Entities:
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Year: 2019 PMID： 30962630 PMCID： PMC8052632 DOI： 10.1038/s41593-019-0370-y
Source DB: PubMed Journal: Nat Neurosci ISSN： 1097-6256 Impact factor: 24.884