Abstract
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.
Highlights
Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide (Siegel et al, 2014)
Myeloid-derived suppressor cells (MDSCs), which often characterized as LinÀCD33+CD11b+HLAÀDRÀ in humans (Ugel et al, 2009), have been reported to be Abbreviations HNSCC, head and neck squamous cell carcinoma; Human papillomavirus (HPV), human papillomavirus; LN, lymph node; mAb, monoclonal antibody; MDSCs, myeloid-derived suppressor cells; TIM3, T-cell immunoglobulin mucin 3; TPF, docetaxel, cisplatin, and fluorouracil; WT, wild-type
An elevated TIM3 expression was consistently found in inflammatory cells of the cancerous tissue (Fig. 1A), and quantification analysis showed the significant up-regulation of TIM3 in HNSCC (n = 122) as compared with dysplasia (n = 43) and normal mucosa (n = 27) (P < 0.05, Fig. 1B)
Summary
Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide (Siegel et al, 2014). Tobacco use and alcohol consumption are the main important risk factors for HNSCC (Argiris et al, 2008). Human papillomavirus (HPV) infection is recognized as another increasing high-risk factor for HNSCC (Marur et al, 2010). Myeloid-derived suppressor cells (MDSCs), which often characterized as LinÀCD33+CD11b+HLAÀDRÀ in humans (Ugel et al, 2009), have been reported to be Abbreviations HNSCC, head and neck squamous cell carcinoma; HPV, human papillomavirus; LN, lymph node; mAb, monoclonal antibody; MDSCs, myeloid-derived suppressor cells; TIM3, T-cell immunoglobulin mucin 3; TPF, docetaxel, cisplatin, and fluorouracil; WT, wild-type
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