免疫系统
免疫检查点
癌症研究
医学
滞后
滞后时间
胶质瘤
单克隆抗体
免疫学
生物
抗体
免疫疗法
胶质母细胞瘤
计算机科学
计算机网络
生物系统
作者
Sarah Harris-Bookman,Dimitrios Mathios,Allison Martin,Yuanxuan Xia,Eileen Kim,Huimin Xu,Zineb Belcaid,Magdalena J. Polanczyk,Theresa J. Barberi,Debebe Theodros,Jennifer Kim,Janis M. Taube,Peter C. Burger,Mark Selby,Corina Taitt,Alan J. Korman,Xiaobu Ye,Charles G. Drake,Henry Brem,Drew M. Pardoll,Michael Lim
摘要
Like in many tumor types, immunotherapy is currently under investigation to assess its potential efficacy in glioblastoma patients. Trials are under way to assess the efficacy of new immune checkpoint inhibitors including anti-PD-1 or CTLA4. We here investigate the expression and efficacy of a novel immune-checkpoint inhibitor, called LAG-3. We show that LAG-3 is expressed in human glioblastoma samples and in a mouse glioblastoma model we show that knock out or LAG-3 inhibition with a blocking antibody is efficacious against glioblastoma and can be used in combination with other immune checkpoint inhibitors toward complete eradication of the model glioblastoma tumors. From a mechanistic standpoint we show that LAG-3 expression is an early marker of T cell exhaustion and therefore early treatment with LAG-3 blocking antibody is more efficacious than later treatment. These data provide insight and support the design of trials that incorporate LAG-3 in the treatment of glioblastoma.
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