T-cell immunoglobulin mucin 3 blockade drives an antitumor immune response in head and neck cancer.
T-cell immunoglobulin mucin 3 blockade drives an antitumor immune response in head and neck cancer.
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T 细胞免疫球蛋白粘蛋白 3 阻断可驱动头颈癌的抗肿瘤免疫反应
DOI：
10.1002/1878-0261.12029
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发表时间：
2017-03
影响因子：
6.6
通讯作者：
Sun ZJ
中科院分区：
文献类型：
--
作者：
Liu JF;Ma SR;Mao L;Bu LL;Yu GT;Li YC;Huang CF;Deng WW;Kulkarni AB;Zhang WF;Sun ZJ
T细胞免疫球蛋白粘蛋白3(TIM3)在许多癌症的进展过程中起免疫抑制作用，但TIM3在头颈部鳞状细胞癌(HNSCC)中的确切作用尚不清楚。在这项研究中，我们报告TIM3在HNSCC患者中的表达显著上调，并与淋巴转移相关。此外，TIM3在复发的HNSCC患者和放疗前或化疗前的患者中表达增加。我们还鉴定了人HNSCC中CD8+T细胞和CD11b+CD33+髓系来源抑制细胞(MDSCs)，发现它们的表达与TIM3的表达呈正相关。为了确定TIM3在HNSCC进展过程中免疫应答的潜在机制，我们利用了TIM3过表达的TGFBR1/Pten 2cKO HNSCC小鼠模型。抗TIM3单抗通过靶向CD4+TIM3+细胞和CD8+TIM3+细胞，减少MDSCs，恢复效应T细胞功能，有效抑制肿瘤生长。我们的发现证实了TIM3在HNSCC患者中的表达，并提示抗TIM3免疫治疗是有效治疗HNSCC的一种新的治疗方法。
T‐cell immunoglobulin mucin 3 (TIM3) contributes to immune suppression during progression of many cancers, but the precise role of TIM3 in head and neck squamous cell carcinoma (HNSCC) is not clearly understood. In this study, we report that TIM3 expression was significantly up‐regulated in patients with HNSCC and associated with lymph node metastasis. Additionally, TIM3 expression was increased in patients with recurrent HNSCC and patients with preradiotherapy or prechemotherapy. We also characterized CD8+ T cells and CD11b+ CD33+ myeloid‐derived suppressor cells (MDSCs) in human HNSCC, and found that their expression was positively correlated with TIM3 expression. To determine the underlying mechanism of TIM3 in immune response during HNSCC progression, we utilized the Tgfbr1/Pten 2cKO HNSCC mouse model with TIM3 overexpression. Treatment with anti‐TIM3 monoclonal antibody effectively suppressed tumor growth through restoring effector T‐cell function by targeting CD4+ TIM3+ cells and CD8+ TIM3+ cells and decreasing MDSCs. Our findings demonstrate TIM3 expression in patients with HNSCC and suggest anti‐TIM3 immunotherapy as a novel therapeutic approach for effective treatment of HNSCC.
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影响因子：
--
作者：
Hervas-Stubbs S;Soldevilla MM;Villanueva H;Mancheño U;Bendandi M;Pastor F
通讯作者：
Pastor F
影响因子：
16.6
作者：
Koyama S;Akbay EA;Li YY;Herter-Sprie GS;Buczkowski KA;Richards WG;Gandhi L;Redig AJ;Rodig SJ;Asahina H;Jones RE;Kulkarni MM;Kuraguchi M;Palakurthi S;Fecci PE;Johnson BE;Janne PA;Engelman JA;Gangadharan SP;Costa DB;Freeman GJ;Bueno R;Hodi FS;Dranoff G;Wong KK;Hammerman PS
通讯作者：
Hammerman PS
DOI：
10.1158/1078-0432.ccr-15-1732
发表时间：
2016-05-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Farren MR;Mace TA;Geyer S;Mikhail S;Wu C;Ciombor K;Tahiri S;Ahn D;Noonan AM;Villalona-Calero M;Bekaii-Saab T;Lesinski GB
通讯作者：
Lesinski GB
影响因子：
8.7
作者：
Freeman GJ;Casasnovas JM;Umetsu DT;DeKruyff RH
通讯作者：
DeKruyff RH
影响因子：
11.2
作者：
Camus, Matthieu;Tosolini, Marie;Galon, Jerome
通讯作者：
Galon, Jerome