STAT1 is regulated by TRIM24 and promotes immunosuppression in head and neck squamous carcinoma cells, but enhances T cell antitumour immunity in the tumour microenvironment.
STAT1 is regulated by TRIM24 and promotes immunosuppression in head and neck squamous carcinoma cells, but enhances T cell antitumour immunity in the tumour microenvironment.
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DOI：
10.1038/s41416-022-01853-z
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发表时间：
2022-09
影响因子：
8.8
通讯作者：
Oghumu, Steve
中科院分区：
文献类型：
--
作者：
Anderson, Kelvin;Ryan, Nathan;Nedungadi, Divya;Lamenza, Felipe;Swingler, Michael;Siddiqui, Arham;Satoskar, Abhay;Upadhaya, Puja;Pietrzak, Maciej;Oghumu, Steve
头颈部鳞状细胞癌(HNSCC)是一个严重的问题，而且经常对现有的治疗方法产生耐药性。STAT1在抗HNSCC的抗肿瘤免疫反应中起重要作用。然而，肿瘤细胞表达STAT1的作用及其在HNSCC过程中的调控尚不清楚。我们在CAL27和UMSCC22A HNSCC细胞系的体外和体内HNSCC致癌物诱导的模型中检测了STAT1抑制对肿瘤生长和免疫的影响。STAT1 siRNA在人HNSCC细胞中的敲除会损害其增殖和免疫抑制标志物PD-L1的表达。在体内肿瘤发生过程中，STAT1基因缺陷小鼠口腔病变发生率和多样性增加。在荷瘤小鼠口腔肿瘤和引流淋巴结中，CD8+T细胞的PD-1和单核细胞MDSCs和巨噬细胞的PD-L1免疫抑制标志物减少。然而，在体内HNSCC过程中，T细胞的抗肿瘤功能需要STAT1。最后，我们确定TRIM24是STAT1的负调控因子，在体外发挥与STAT1相似的致瘤作用，因此可能成为治疗HNSCC的潜在靶点。我们的研究结果表明，STAT1活性在HNSCC的发生和免疫抑制中起重要作用。
Head and neck squamous cell carcinoma (HNSCC) is a significant problem and is frequently resistant to current treatments. STAT1 is important in anti-tumour immune responses against HNSCC. However, the role of STAT1 expression by tumour cells and its regulation during HNSCC is unclear. We determined the effects of STAT1 inhibition on tumour development and immunity in CAL27 and UMSCC22A HNSCC cell lines in vitro and in a HNSCC carcinogen-induced model in vivo. STAT1 siRNA knockdown in human HNSCC cells impaired their proliferation and expression of the immunosuppressive marker PD-L1. Stat1-deficient mice displayed increased oral lesion incidence and multiplicity during tumour carcinogenesis in vivo. Immunosuppressive markers PD-1 in CD8+ T cells and PD-L1 in monocytic MDSCs and macrophages were reduced in oral tumours and draining lymph nodes of tumour-bearing Stat1-deficient mice. However, STAT1 was required for anti-tumour functions of T cells during HNSCC in vivo. Finally, we identified TRIM24 to be a negative regulator of STAT1 that plays a similar tumorigenic function to STAT1 in vitro and thus may be a potential target when treating HNSCC. Our findings indicate that STAT1 activity plays an important role in tumorigenicity and immunosuppression during HNSCC development.
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影响因子：
2.3
作者：
El Jamal SM;Taylor EB;Abd Elmageed ZY;Alamodi AA;Selimovic D;Alkhateeb A;Hannig M;Hassan SY;Santourlidis S;Friedlander PL;Haikel Y;Vijaykumar S;Kandil E;Hassan M
通讯作者：
Hassan M
DOI：
10.1186/s13046-019-1256-2
发表时间：
2019-06-10
影响因子：
11.3
作者：
Chang, Wei-Min;Chang, Yu-Chan;Hsiao, Michael
通讯作者：
Hsiao, Michael
DOI：
10.4049/jimmunol.1202714
发表时间：
2013-07-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Fortin C;Huang X;Yang Y
通讯作者：
Yang Y
DOI：
10.1007/s00262-010-0961-7
发表时间：
2011-04
期刊：
Cancer immunology, immunotherapy : CII
影响因子：
--
作者：
Leibowitz MS;Andrade Filho PA;Ferrone S;Ferris RL
通讯作者：
Ferris RL
DOI：
10.4161/jkst.24198
发表时间：
2013-01-01
期刊：
JAK-STAT
影响因子：
--
作者：
Kaplan MH
通讯作者：
Kaplan MH