Idioma:

CD155T/TIGIT Signaling Regulates CD8 + T-cell Metabolism and Promotes Tumor Progression in Human Gastric Cancer

He, Weiling ; Zhang, Hui ; Han, Fei ; Chen, Xinlin ; Lin, Run ; Wang, Wei ; Qiu, Haibo ; Zhuang, Zhenhong ; Liao, Qi ; Zhang, Weijing ; Cai, Qinbo ; Cui, Yongmei ; Jiang, Wenting ; Wang, Han ; Ke, Zunfu

Cancer research (Chicago, Ill.), 2017-11, Vol.77 (22), p.6375-6388 [Periódico revisado por pares]

United States: American Association for Cancer Research, Inc

Texto completo disponível

Citações Citado por

Enviar para

Título:
CD155T/TIGIT Signaling Regulates CD8 + T-cell Metabolism and Promotes Tumor Progression in Human Gastric Cancer
Autor: He, Weiling ; Zhang, Hui ; Han, Fei ; Chen, Xinlin ; Lin, Run ; Wang, Wei ; Qiu, Haibo ; Zhuang, Zhenhong ; Liao, Qi ; Zhang, Weijing ; Cai, Qinbo ; Cui, Yongmei ; Jiang, Wenting ; Wang, Han ; Ke, Zunfu
Assuntos: Animals ; CD8 antigen ; CD8-Positive T-Lymphocytes - drug effects ; CD8-Positive T-Lymphocytes - immunology ; CD8-Positive T-Lymphocytes - metabolism ; Cell activation ; Cell culture ; Cell Line, Tumor ; Cell proliferation ; Cell surface ; Cell survival ; Cells, Cultured ; Coculture Techniques ; Disease Progression ; Exhaustion ; Gastric cancer ; Glucose ; Glucose - pharmacology ; Humans ; Immune checkpoint ; Lymphocytes ; Lymphocytes T ; Metabolism ; Mice ; Mice, Inbred NOD ; Mice, Knockout ; Mice, SCID ; PD-1 protein ; Receptors, Immunologic - genetics ; Receptors, Immunologic - immunology ; Receptors, Immunologic - metabolism ; Receptors, Virus - genetics ; Receptors, Virus - immunology ; Receptors, Virus - metabolism ; RNA Interference ; Signal Transduction - genetics ; Signal Transduction - immunology ; Stomach Neoplasms - genetics ; Stomach Neoplasms - immunology ; Stomach Neoplasms - metabolism ; Survival Analysis ; T cell receptors ; T-Lymphocytes - immunology ; T-Lymphocytes - metabolism ; Tumor cell lines ; Tumor cells ; Xenograft Model Antitumor Assays - methods ; γ-Interferon
É parte de: Cancer research (Chicago, Ill.), 2017-11, Vol.77 (22), p.6375-6388
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
Descrição: The T-cell surface molecule TIGIT is an immune checkpoint molecule that inhibits T-cell responses, but its roles in cancer are little understood. In this study, we evaluated the role TIGIT checkpoint plays in the development and progression of gastric cancer. We show that the percentage of CD8 T cells that are TIGIT was increased in gastric cancer patients compared with healthy individuals. These cells showed functional exhaustion with impaired activation, proliferation, cytokine production, and metabolism, all of which were rescued by glucose. In addition, gastric cancer tissue and cell lines expressed CD155, which bound TIGIT receptors and inactivated CD8 T cells. In a T cell-gastric cancer cell coculture system, gastric cancer cells deprived CD8 T cells of glucose and impaired CD8 T-cell effector functions; these effects were neutralized by the additional glucose or by TIGIT blockade. In gastric cancer tumor cells, CD155 silencing increased T-cell metabolism and IFNγ production, whereas CD155 overexpression inhibited T-cell metabolism and IFNγ production; this inhibition was neutralized by TIGIT blockade. Targeting CD155/TIGIT enhanced CD8 T-cell reaction and improved survival in tumor-bearing mice. Combined targeting of TIGIT and PD-1 further enhanced CD8 T-cell activation and improved survival in tumor-bearing mice. Our results suggest that gastric cancer cells inhibit CD8 T-cell metabolism through CD155/TIGIT signaling, which inhibits CD8 T-cell effector functions, resulting in hyporesponsive antitumor immunity. These findings support the candidacy of CD155/TIGIT as a potential therapeutic target in gastric cancer. .
Editor: United States: American Association for Cancer Research, Inc
Idioma: Inglês

Links

View this record in MEDLINE/PubMed

Voltar para lista de resultados

Resultado 1 Avançar Ir para próxima página

Realização: Logos de Redes Sociais:

CD155T/TIGIT Signaling Regulates CD8 + T-cell Metabolism and Promotes Tumor Progression in Human Gastric Cancer

He, Weiling ; Zhang, Hui ; Han, Fei ; Chen, Xinlin ; Lin, Run ; Wang, Wei ; Qiu, Haibo ; Zhuang, Zhenhong ; Liao, Qi ; Zhang, Weijing ; Cai, Qinbo ; Cui, Yongmei ; Jiang, Wenting ; Wang, Han ; Ke, Zunfu

United States: American Association for Cancer Research, Inc

Buscando em bases de dados remotas. Favor aguardar.