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CLIN CANCER RES :抗原呈递后BTLA对CD8+T细胞具有多种作用

2017-10-29 MedSci MedSci原创

利用自体肿瘤浸润淋巴细胞(TIL)进行过继T细胞治疗在转移性黑色素瘤患者中总临床反应率在40%-50%。输入的CD8+肿瘤浸润淋巴细胞BTLA表达与更好的临床结局有关。CLIN CANCER RES近期发表了一篇文章,研究CD8+BTLA+TIL亚群的功能特点以及BTLA中的Grb2在T细胞共刺激中发挥的作用。

利用自体肿瘤浸润淋巴细胞(TIL)进行过继T细胞治疗在转移性黑色素瘤患者中总临床反应率在40%-50%。输入的CD8+肿瘤浸润淋巴细胞BTLA表达与更好的临床结局有关。CLIN CANCER RES近期发表了一篇文章,研究CD8+BTLA+TIL亚群的功能特点以及BTLA中的Grb2在T细胞共刺激中发挥的作用。

作者在人CD8+TIL和鼠CD8+T细胞中研究BTLA发挥的作用及BTLA下游信号。使用的功能研究方法包括单细胞分析,RPPA,抗原特异性疫苗模型联合过继TCR转基因T细胞以及使用免疫缺陷NSG肿瘤负荷鼠构建PDX模型并使用自体TIL细胞进行干预。研究结果表明,CD8+BTLA-TIL细胞在体内不能控制肿瘤生长,抗原特异性CD8+BTLA-T细胞对疫苗的反应受损。但是,CD8+BTLA+TIL细胞在杀伤肿瘤靶标后生存期延长并且持续杀伤能力得到提升。研究还发现Grb2通过增强IL-2分泌和TCR激活后Src活化调节共刺激功能。

文章最后认为,BTLA作为分子具有对已激活的CD8+T细胞同时提供共刺激和共抑制信号的能力,可以导致细胞生存期延长,改善肿瘤控制情况以及产生功能性记忆应答

原始出处:
Krit Ritthipichai,Cara L.Haymaker,et al.Multifaceted Role of BTLA in the Control of CD8+ T-cell Fate after Antigen Encounter.CLIN CANCER RES.October 2017 doi:10.1158/1078-0432.CCR-16-1217

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    2018-03-30 gds2009
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    2017-10-29 天涯183

    非常好的文章.学习了

    0

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    2017-10-29 131****1460

    学习了受益匪浅

    0

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