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T‐cell immunoglobulin mucin 3 blockade drives an antitumor immune response in head and neck cancer

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...

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Autores principales: Liu, Jian‐Feng, Ma, Si‐Rui, Mao, Liang, Bu, Lin‐Lin, Yu, Guang‐Tao, Li, Yi‐Cun, Huang, Cong‐Fa, Deng, Wei‐Wei, Kulkarni, Ashok B., Zhang, Wen‐Feng, Sun, Zhi‐Jun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5527458/
https://www.ncbi.nlm.nih.gov/pubmed/28102051
http://dx.doi.org/10.1002/1878-0261.12029
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author Liu, Jian‐Feng
Ma, Si‐Rui
Mao, Liang
Bu, Lin‐Lin
Yu, Guang‐Tao
Li, Yi‐Cun
Huang, Cong‐Fa
Deng, Wei‐Wei
Kulkarni, Ashok B.
Zhang, Wen‐Feng
Sun, Zhi‐Jun
author_facet Liu, Jian‐Feng
Ma, Si‐Rui
Mao, Liang
Bu, Lin‐Lin
Yu, Guang‐Tao
Li, Yi‐Cun
Huang, Cong‐Fa
Deng, Wei‐Wei
Kulkarni, Ashok B.
Zhang, Wen‐Feng
Sun, Zhi‐Jun
author_sort Liu, Jian‐Feng
collection PubMed
description 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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spelling pubmed-55274582017-08-15 T‐cell immunoglobulin mucin 3 blockade drives an antitumor immune response in head and neck cancer Liu, Jian‐Feng Ma, Si‐Rui Mao, Liang Bu, Lin‐Lin Yu, Guang‐Tao Li, Yi‐Cun Huang, Cong‐Fa Deng, Wei‐Wei Kulkarni, Ashok B. Zhang, Wen‐Feng Sun, Zhi‐Jun Mol Oncol Research Articles 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. John Wiley and Sons Inc. 2017-01-19 2017-02 /pmc/articles/PMC5527458/ /pubmed/28102051 http://dx.doi.org/10.1002/1878-0261.12029 Text en © 2016 The Authors. Published by FEBS Press and John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Articles
Liu, Jian‐Feng
Ma, Si‐Rui
Mao, Liang
Bu, Lin‐Lin
Yu, Guang‐Tao
Li, Yi‐Cun
Huang, Cong‐Fa
Deng, Wei‐Wei
Kulkarni, Ashok B.
Zhang, Wen‐Feng
Sun, Zhi‐Jun
T‐cell immunoglobulin mucin 3 blockade drives an antitumor immune response in head and neck cancer
title T‐cell immunoglobulin mucin 3 blockade drives an antitumor immune response in head and neck cancer
title_full T‐cell immunoglobulin mucin 3 blockade drives an antitumor immune response in head and neck cancer
title_fullStr T‐cell immunoglobulin mucin 3 blockade drives an antitumor immune response in head and neck cancer
title_full_unstemmed T‐cell immunoglobulin mucin 3 blockade drives an antitumor immune response in head and neck cancer
title_short T‐cell immunoglobulin mucin 3 blockade drives an antitumor immune response in head and neck cancer
title_sort t‐cell immunoglobulin mucin 3 blockade drives an antitumor immune response in head and neck cancer
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5527458/
https://www.ncbi.nlm.nih.gov/pubmed/28102051
http://dx.doi.org/10.1002/1878-0261.12029
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