T‐cell immunoglobulin mucin 3 blockade drives an antitumor immune response in head and neck cancer
نویسندگان
چکیده
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.
منابع مشابه
Blockade of TIM3 relieves immunosuppression through reducing regulatory T cells in head and neck cancer
BACKGROUND T-cell immunoglobulin mucin 3 (TIM3) is a negative immune checkpoint and plays a crucial part in tumor-induced immune suppression. However, the mechanism of TIM3 in regulating immunosuppression in head and neck squamous cell carcinoma (HNSCC) was still not quite clear. METHODS We carried out the immunohistochemistry staining of HNSCC tissue microarrays. Through quantification of th...
متن کاملPreparation and characterization of a novel nanobody against T-cell immunoglobulin and mucin-3 (TIM-3)
Objective(s): As T-cell immunoglobulin and mucin domain 3 (TIM-3) is an immune regulatory molecule; its blocking or stimulating could alter the pattern of immune response towards a desired condition. Based on the unique features of nanobodies, we aimed to construct an anti-TIM-3 nanobody as an appropriate tool for manipulating immune responses for future therapeutic purposes. Materials and Meth...
متن کاملReversal of NK-cell exhaustion in advanced melanoma by Tim-3 blockade.
The immunoregulatory protein T-cell immunoglobulin- and mucin-domain-containing molecule-3 (Tim-3) mediates T-cell exhaustion and contributes to the suppression of immune responses in both viral infections and tumors. Tim-3 blockade reverses the exhausted phenotype of CD4+ and CD8+ T cells in several chronic diseases, including melanoma. Interestingly, natural killer (NK) cells constitutively e...
متن کاملT cell immunoglobulin domain and mucin domain-3 as an emerging target for immunotherapy in cancer management
Cancer-induced immunosuppression significantly impacts tumors, rendering them the ability to acquire aggressive and treatment-resistant phenotypes. The recent clinical success of drugs targeting the immunosuppressive machinery of tumors highlights the importance of identifying novel drugs that effectively augment antitumor immunity and elicit clinical remission in advanced tumors. T cell immuno...
متن کاملTIM3+FOXP3+ regulatory T cells are tissue-specific promoters of T-cell dysfunction in cancer
T-cell immunoglobulin mucin 3 (TIM3) is an inhibitory molecule that has emerged as a key regulator of dysfunctional or exhausted CD8+ T cells arising in chronic diseases such as cancer. In addition to exhausted CD8+ T cells, highly suppressive regulatory T cells (Tregs) represent a significant barrier against the induction of antitumor immunity. We have found that the majority of intratumoral F...
متن کامل