PD-1 Blockade on Tumor Microenvironment-Resident ILC2s Promotes TNF-α Production and Restricts Progression of Metastatic Melanoma.

PD-1 Blockade on Tumor Microenvironment-Resident ILC2s Promotes TNF-α Production and Restricts Progression of Metastatic Melanoma.
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DOI:
10.3389/fimmu.2021.733136
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发表时间:
2021
影响因子:
7.3
通讯作者:
Akbari O
Akbari O
中科院分区:
医学2区
文献类型:
--
作者:
Howard E;Hurrell BP;Helou DG;Quach C;Painter JD;Shafiei-Jahani P;Fung M;Gill PS;Soroosh P;Sharpe AH;Akbari O

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虽然肺部ILC 2代表了稳态时主要的组织驻留先天淋巴样细胞群体之一,并且是其职业生态位中细胞因子分泌的关键驱动因素,但其在肺癌进展中的作用仍不清楚。由于程序性细胞死亡蛋白-1(PD-1)在癌症免疫治疗和免疫调节特性中起着重要作用,因此我们研究了PD-1抑制对肺B16黑色素瘤癌转移过程中ILC 2的特异性影响。我们证明PD-1对ILC 2的抑制抑制B16肿瘤生长。此外,PD-1抑制上调肺ILC 2衍生的TNF-α产生,这是一种直接诱导B16细胞细胞死亡的细胞毒性细胞因子,与适应性免疫无关。总之,这些结果突出了ILC 2的重要性及其在PD-1抑制性免疫治疗期间在肺部B16癌症进展中的抗肿瘤作用。
While pulmonary ILC2s represent one of the major tissue-resident innate lymphoid cell populations at steady state and are key drivers of cytokine secretion in their occupational niche, their role in pulmonary cancer progression remains unclear. As the programmed cell death protein-1 (PD-1) plays a major role in cancer immunotherapy and immunoregulatory properties, here we investigate the specific effect of PD-1 inhibition on ILC2s during pulmonary B16 melanoma cancer metastasis. We demonstrate that PD-1 inhibition on ILC2s suppresses B16 tumor growth. Further, PD-1 inhibition upregulates pulmonary ILC2-derived TNF-α production, a cytotoxic cytokine that directly induces cell death in B16 cells, independent of adaptive immunity. Together, these results highlight the importance of ILC2s and their anti-tumor role in pulmonary B16 cancer progression during PD-1 inhibitory immunotherapy.
Juzentaihoto 对 B16 黑色素瘤转移模型中肿瘤免疫治疗的功效。
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