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Overexpression of TIGIT in NK and T Cells Contributes to Tumor Immune Escape in Myelodysplastic Syndromes

OBJECTIVE: Targeting immune checkpoints, such as PD-1, represents a promising approach for cancer immunotherapy, achieving long-term disease remission rates in numerous types of cancer. T cell immunoglobulin and ITIM domain (TIGIT) is a checkpoint receptor associated with the antitumor roles of NK a...

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Autores principales: Meng, Fanqiao, Li, Lijuan, Lu, Fengzhu, Yue, Jing, Liu, Zhaoyun, Zhang, Wei, Fu, Rong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7438899/
https://www.ncbi.nlm.nih.gov/pubmed/32903786
http://dx.doi.org/10.3389/fonc.2020.01595
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author Meng, Fanqiao
Li, Lijuan
Lu, Fengzhu
Yue, Jing
Liu, Zhaoyun
Zhang, Wei
Fu, Rong
author_facet Meng, Fanqiao
Li, Lijuan
Lu, Fengzhu
Yue, Jing
Liu, Zhaoyun
Zhang, Wei
Fu, Rong
author_sort Meng, Fanqiao
collection PubMed
description OBJECTIVE: Targeting immune checkpoints, such as PD-1, represents a promising approach for cancer immunotherapy, achieving long-term disease remission rates in numerous types of cancer. T cell immunoglobulin and ITIM domain (TIGIT) is a checkpoint receptor associated with the antitumor roles of NK and T cells. Notably, the blockade of TIGIT has been revealed as a potential promising approach in cancer immunotherapy. However, the therapeutic potential of blocking TIGIT in myelodysplastic syndrome (MDS) remains unclear and further research is required to reveal their role. METHODS: Fresh peripheral blood (PB) and bone marrow (BM) were obtained from patients with MDS and healthy donors (HDs) at the Tianjin Medical University General Hospital between January 21 2018 and March 22 2019. The present study investigated the expression levels of TIGIT on NK and T cells using flow cytometry (FCM) and PCR. In addition, other checkpoint receptors, such as CD226 and PD-1, were also investigated. To determine the mechanisms of antitumor immunity, the functions of NK and T cells expressing TIGIT were determined. RESULTS: TIGIT was found to be highly expressed on NK and T cells of the PB, where it was involved in disease progression and the immune escape of MDS. The high expression levels of TIGIT were associated with decreased NK and T cell function, and significantly lower secretions of activation factors, such as CD107a, IFN-γ and TNF-α. Notably, blocking TIGIT enhanced the antitumor effects of NK and T cells. CONCLUSION: The results of the present study suggested that targeting TIGIT alone or in combination with PD-1 may be a promising anticancer therapeutic strategy in MDS.
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spelling pubmed-74388992020-09-03 Overexpression of TIGIT in NK and T Cells Contributes to Tumor Immune Escape in Myelodysplastic Syndromes Meng, Fanqiao Li, Lijuan Lu, Fengzhu Yue, Jing Liu, Zhaoyun Zhang, Wei Fu, Rong Front Oncol Oncology OBJECTIVE: Targeting immune checkpoints, such as PD-1, represents a promising approach for cancer immunotherapy, achieving long-term disease remission rates in numerous types of cancer. T cell immunoglobulin and ITIM domain (TIGIT) is a checkpoint receptor associated with the antitumor roles of NK and T cells. Notably, the blockade of TIGIT has been revealed as a potential promising approach in cancer immunotherapy. However, the therapeutic potential of blocking TIGIT in myelodysplastic syndrome (MDS) remains unclear and further research is required to reveal their role. METHODS: Fresh peripheral blood (PB) and bone marrow (BM) were obtained from patients with MDS and healthy donors (HDs) at the Tianjin Medical University General Hospital between January 21 2018 and March 22 2019. The present study investigated the expression levels of TIGIT on NK and T cells using flow cytometry (FCM) and PCR. In addition, other checkpoint receptors, such as CD226 and PD-1, were also investigated. To determine the mechanisms of antitumor immunity, the functions of NK and T cells expressing TIGIT were determined. RESULTS: TIGIT was found to be highly expressed on NK and T cells of the PB, where it was involved in disease progression and the immune escape of MDS. The high expression levels of TIGIT were associated with decreased NK and T cell function, and significantly lower secretions of activation factors, such as CD107a, IFN-γ and TNF-α. Notably, blocking TIGIT enhanced the antitumor effects of NK and T cells. CONCLUSION: The results of the present study suggested that targeting TIGIT alone or in combination with PD-1 may be a promising anticancer therapeutic strategy in MDS. Frontiers Media S.A. 2020-08-07 /pmc/articles/PMC7438899/ /pubmed/32903786 http://dx.doi.org/10.3389/fonc.2020.01595 Text en Copyright © 2020 Meng, Li, Lu, Yue, Liu, Zhang and Fu. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Meng, Fanqiao
Li, Lijuan
Lu, Fengzhu
Yue, Jing
Liu, Zhaoyun
Zhang, Wei
Fu, Rong
Overexpression of TIGIT in NK and T Cells Contributes to Tumor Immune Escape in Myelodysplastic Syndromes
title Overexpression of TIGIT in NK and T Cells Contributes to Tumor Immune Escape in Myelodysplastic Syndromes
title_full Overexpression of TIGIT in NK and T Cells Contributes to Tumor Immune Escape in Myelodysplastic Syndromes
title_fullStr Overexpression of TIGIT in NK and T Cells Contributes to Tumor Immune Escape in Myelodysplastic Syndromes
title_full_unstemmed Overexpression of TIGIT in NK and T Cells Contributes to Tumor Immune Escape in Myelodysplastic Syndromes
title_short Overexpression of TIGIT in NK and T Cells Contributes to Tumor Immune Escape in Myelodysplastic Syndromes
title_sort overexpression of tigit in nk and t cells contributes to tumor immune escape in myelodysplastic syndromes
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7438899/
https://www.ncbi.nlm.nih.gov/pubmed/32903786
http://dx.doi.org/10.3389/fonc.2020.01595
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