Control of tumor-associated macrophages and T cells in glioblastoma via AHR and CD39.
Control of tumor-associated macrophages and T cells in glioblastoma via AHR and CD39.
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DOI：
10.1038/s41593-019-0370-y
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发表时间：
2019-05
影响因子：
25
通讯作者：
Quintana FJ
中科院分区：
文献类型：
--
作者：
Takenaka MC;Gabriely G;Rothhammer V;Mascanfroni ID;Wheeler MA;Chao CC;Gutiérrez-Vázquez 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;Prat A;Antel J;Reardon DA;Zhang H;Robson SC;Getz G;Weiner HL;Quintana FJ
肿瘤相关巨噬细胞（TAM）在对癌症的免疫应答中起着重要作用，但肿瘤微环境控制TAM和T细胞免疫的机制尚未完全了解。在这里，我们报告了由胶质母细胞瘤细胞产生的犬尿氨酸激活TAM中的芳烃受体（AHR）以调节其功能和T细胞免疫。AHR促进CCR 2表达，驱动TAM募集以响应CCL 2。AHR还驱动KLF 4的表达并抑制TAM中NF-κB的活化。最后，AHR驱动TAM中外核苷酸酶CD 39的表达，其通过与CD 73合作产生腺苷来促进CD 8 + T细胞功能障碍。在人类中，AHR和CD 39在4级胶质瘤中表达最高，并且高AHR表达与不良预后相关。总之，TAM中表达的AHR和CD 39参与胶质母细胞瘤中免疫应答的调节，并构成免疫治疗的潜在靶点。
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.
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DOI：
10.1016/j.tem.2017.02.009
发表时间：
2017-06
期刊：
Trends in endocrinology and metabolism: TEM
影响因子：
--
作者：
Gabriely G;Wheeler MA;Takenaka MC;Quintana FJ
通讯作者：
Quintana FJ
影响因子：
64.8
作者：
De Henau O;Rausch M;Winkler D;Campesato LF;Liu C;Cymerman DH;Budhu S;Ghosh A;Pink M;Tchaicha J;Douglas M;Tibbitts T;Sharma S;Proctor J;Kosmider N;White K;Stern H;Soglia J;Adams J;Palombella VJ;McGovern K;Kutok JL;Wolchok JD;Merghoub T
通讯作者：
Merghoub T
影响因子：
82.9
作者：
通讯作者：
--
影响因子：
64.5
作者：
Gosselin D;Link VM;Romanoski CE;Fonseca GJ;Eichenfield DZ;Spann NJ;Stender JD;Chun HB;Garner H;Geissmann F;Glass CK
通讯作者：
Glass CK
影响因子：
32.4
作者：
Noy, Roy;Pollard, Jeffrey W.
通讯作者：
Pollard, Jeffrey W.