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LAG-3 expression on tumor-infiltrating T cells in soft tissue sarcoma correlates with poor survival

OBJECTIVE: To elucidate the role and prognostic significance of lymphocyte activation-gene-3 (LAG-3) in soft tissue sarcoma (STS). METHODS: The expression of LAG-3 in patient and matched normal blood samples was analyzed by flow cytometry. The localization and prognostic values of LAG-3(+) cells in...

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Detalles Bibliográficos
Autores principales: Que, Yi, Fang, Zhixin, Guan, Yuanxiang, Xiao, Wei, Xu, Bushu, Zhao, Jingjing, Chen, Huoying, Zhang, Xinke, Zeng, Musheng, Liang, Yao, Zhang, Xing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Chinese Anti-Cancer Association 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6713642/
https://www.ncbi.nlm.nih.gov/pubmed/31516753
http://dx.doi.org/10.20892/j.issn.2095-3941.2018.0306
Descripción
Sumario:OBJECTIVE: To elucidate the role and prognostic significance of lymphocyte activation-gene-3 (LAG-3) in soft tissue sarcoma (STS). METHODS: The expression of LAG-3 in patient and matched normal blood samples was analyzed by flow cytometry. The localization and prognostic values of LAG-3(+) cells in 163 STS patients were analyzed by immunohistochemistry. In addition, the expression of tumor-infiltrating CD3(+) T, CD4(+) T, and CD8(+) T cells and their role in the prognosis of STS were evaluated by immunohistochemistry. The effect of LAG-3 blockade was evaluated in an immunocompetent MCA205 fibrosarcoma mouse model. RESULTS: Peripheral CD8(+) and CD4(+) T cells from STS patients expressed higher levels of LAG-3 than those from healthy donors. LAG-3 expression in STS was significantly associated with a poor clinical outcome (P = 0.038 ) and was correlated with high pathological grade (P < 0.001), advanced tumor stage ( P = 0.016). Additionally, LAG-3 expression was highly correlated with CD8(+) T-cell infiltration (r = 0.7034, P < 0.001). LAG-3 was expressed in murine tumor-infiltrating lymphocytes, and its blockade decreased tumor growth and enhanced secretion of interferon-gamma by CD8 (+) and CD4(+) T cells. CONCLUSIONS: LAG-3 blockade may be a promising strategy to improve the effects of targeted therapy in STS.