CELL:降低肿瘤TNF毒性阈值可增强免疫疗法效果

2019-07-16 海北 MedSci原创

在最近的一项研究中,利用全基因组CRISPR / Cas9进行筛选,使IFNγ受体缺陷的肿瘤细胞对CD8 T细胞消除敏感,研究人员发现了几种映射到肿瘤坏死因子(TNF)途径的基因。

现有的发展表明,我们需要新的机会来增加免疫检查点封锁(ICB)的益处。

尽管干扰素(IFNγ途径同时具有ICB抗性因子和治疗机会,但至今为止,我们尚未系统地研究IFNγ非依赖性信号传导途径。

在最近的一项研究中,利用全基因组CRISPR / Cas9进行筛选,使IFNγ受体缺陷的肿瘤细胞对CD8 T细胞消除敏感,研究人员发现了几种映射到肿瘤坏死因子(TNF)途径的基因。

临床上,结果显示,TNF抗肿瘤活性仅限于基线和ICB无应答者的肿瘤,与其低丰度相关。

利用遗传筛选,研究人员证明,筛选中最高分基因TRAF2的消融通过重定向TNF信号传导,有利于RIPK1依赖性细胞凋亡,从而降低肿瘤中的TNF细胞毒性阈值。 

TRAF2的缺失大大增强了其相互作用伴侣cIAP的药理学抑制的治疗潜力,从而与ICB合作发挥作用。

因此,该结果表明,选择性降低TNF细胞毒性阈值增加了肿瘤对免疫疗法的易感性。


原始出处:

Vredevoogd DW et al. Augmenting Immunotherapy Impact by Lowering Tumor TNF Cytotoxicity Threshold. CELL, 2019; doi: 10.1016/j.cell.2019.06.014.


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    2019-09-02 zhaojie88
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    2020-06-11 维他命
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    2019-07-18 snowpeakxu
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    2019-07-18 qjddjq
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    2019-07-17 CHANGE

    疗效只是效果的众多方面之一,还要看对患者的获益,包括生活质量等因素共同决定效果的

    0

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