The Role of Dectin-1 Signaling in Altering Tumor Immune Microenvironment in the Context of Aging.
The Role of Dectin-1 Signaling in Altering Tumor Immune Microenvironment in the Context of Aging.
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DOI：
10.3389/fonc.2021.669066
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发表时间：
2021
影响因子：
4.7
通讯作者：
Pandiyan P
中科院分区：
文献类型：
--
作者：
Bhaskaran N;Jayaraman S;Quigley C;Mamileti P;Ghannoum M;Weinberg A;Thuener J;Pan Q;Pandiyan P
在感染期间，在老化的口腔黏膜中观察到免疫功能障碍相关CD4+Foxp3+调节性T细胞（Tregs）的积累增加。我们研究了Tregs在口腔癌老化黏膜发生过程中的作用。首先，我们发现Tregs和髓源性抑制细胞（MDSC）在小鼠和人口腔鳞状细胞癌（OSCC）组织中积累的比例升高。通过小鼠4-硝基喹啉-1 -氧化物（4-NQO）口腔癌模型，我们发现老龄小鼠的舌头上皮细胞发育不良、增生的倾向增加，OSCC的发展加速，同时舌头中IL-1β、Tregs和MDSC的丰度显著增加。Tregs的部分耗竭减少了肿瘤负荷。此外，真菌丰度和dectin-1信号在老年小鼠中升高，表明dectin-1在调节免疫环境和肿瘤发展中可能起作用。证实了这一原则，dectin-1缺陷小鼠表现出IL-1β减少，Tregs和MDSC在舌头中的浸润减少，肿瘤进展缓慢，肿瘤负担严重程度降低。综上所述，这些数据确定了dectin-1信号在建立肿瘤内免疫抑制环境和促进衰老背景下OSCC肿瘤发生中的重要作用。
An increased accumulation of immune-dysfunction-associated CD4+Foxp3+ regulatory T cells (Tregs) is observed in aging oral mucosa during infection. Here we studied the function of Tregs during oral cancer development in aging mucosa. First, we found heightened proportions of Tregs and myeloid-derived suppressor cells (MDSC) accumulating in mouse and human oral squamous cell carcinoma (OSCC) tissues. Using the mouse 4-Nitroquinoline 1-oxide(4-NQO) oral carcinogenesis model, we found that tongues of aged mice displayed increased propensity for epithelial cell dysplasia, hyperplasia, and accelerated OSCC development, which coincided with significantly increased abundance of IL-1β, Tregs, and MDSC in tongues. Partial depletion of Tregs reduced tumor burden. Moreover, fungal abundance and dectin-1 signaling were elevated in aged mice suggesting a potential role for dectin-1 in modulating immune environment and tumor development. Confirming this tenet, dectin-1 deficient mice showed diminished IL-1β, reduced infiltration of Tregs and MDSC in the tongues, as well as slower progression and reduced severity of tumor burden. Taken together, these data identify an important role of dectin-1 signaling in establishing the intra-tumoral immunosuppressive milieu and promoting OSCC tumorigenesis in the context of aging.
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影响因子：
16.6
作者：
Downs-Canner S;Berkey S;Delgoffe GM;Edwards RP;Curiel T;Odunsi K;Bartlett DL;Obermajer N
通讯作者：
Obermajer N
影响因子：
9.2
作者：
Dinarello, Charles A.
通讯作者：
Dinarello, Charles A.
DOI：
10.1177/003591576906200637
发表时间：
1969-01-01
期刊：
PROCEEDINGS OF THE ROYAL SOCIETY OF MEDICINE-LONDON
影响因子：
--
作者：
CAWSON, RA
通讯作者：
CAWSON, RA
影响因子：
5.5
作者：
Cheng SC;van de Veerdonk FL;Lenardon M;Stoffels M;Plantinga T;Smeekens S;Rizzetto L;Mukaremera L;Preechasuth K;Cavalieri D;Kanneganti TD;van der Meer JW;Kullberg BJ;Joosten LA;Gow NA;Netea MG
通讯作者：
Netea MG
影响因子：
3.7
作者：
Barchiesi F;Orsetti E;Mazzanti S;Trave F;Salvi A;Nitti C;Manso E
通讯作者：
Manso E