A nanounit strategy reverses immune suppression of exosomal PD-L1 and is associated with enhanced ferroptosis.
A nanounit strategy reverses immune suppression of exosomal PD-L1 and is associated with enhanced ferroptosis.
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DOI：
10.1038/s41467-021-25990-w
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发表时间：
2021-09-30
影响因子：
16.6
通讯作者：
Dai Y
中科院分区：
文献类型：
--
作者：
Wang G;Xie L;Li B;Sang W;Yan J;Li J;Tian H;Li W;Zhang Z;Tian Y;Dai Y
肿瘤细胞除了增加程序性死亡配体1（PD-L1）的表达外，还可以分泌外泌体PD-L1来抑制T细胞活性。新的证据表明，外泌体 PD-L1 可以抵抗免疫检查点阻断，并可能导致对治疗的抵抗。在这种情况下，抑制肿瘤源性外泌体的分泌可能有助于治疗。在这里，我们通过两亲性透明质酸开发了外泌体抑制剂（GW4869）和铁死亡诱导剂（Fe3+）的组装体。所构建的纳米单元中两种活性成分之间的协同作用可诱导针对 B16F10 黑色素瘤细胞的抗肿瘤免疫反应，并刺激细胞毒性 T 淋巴细胞和免疫记忆。该纳米单元增强了对 PD-L1 检查点阻断的反应，并且可能代表增强对该疗法的反应的治疗策略。 PD-L1经常在癌细胞表面表达，并且可以通过外泌体从癌细胞中分泌出来。在这里，作者开发了一种纳米疗法，结合了外泌体产生的抑制剂和铁死亡的诱导剂，增强了对免疫检查点阻断疗法的反应。
In addition to increasing the expression of programmed death-ligand 1 (PD-L1), tumor cells can also secrete exosomal PD-L1 to suppress T cell activity. Emerging evidence has revealed that exosomal PD-L1 resists immune checkpoint blockade, and may contribute to resistance to therapy. In this scenario, suppressing the secretion of tumor-derived exosomes may aid therapy. Here, we develop an assembly of exosome inhibitor (GW4869) and ferroptosis inducer (Fe3+) via amphiphilic hyaluronic acid. Cooperation between the two active components in the constructed nanounit induces an anti-tumor immunoresponse to B16F10 melanoma cells and stimulates cytotoxic T lymphocytes and immunological memory. The nanounit enhances the response to PD-L1 checkpoint blockade and may represent a therapeutic strategy for enhancing the response to this therapy. PD-L1 is frequently expressed on the surface of cancer cells and can be excreted from cancer cells in exosomes. Here, the authors generate a nanotherapy that combines an inhibitor of exosome production and an inducer of ferroptosis, enhancing the response to immune checkpoint blockade therapy.
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影响因子：
64.5
作者：
Dixon SJ;Lemberg KM;Lamprecht MR;Skouta R;Zaitsev EM;Gleason CE;Patel DN;Bauer AJ;Cantley AM;Yang WS;Morrison B 3rd;Stockwell BR
通讯作者：
Stockwell BR
头颈癌患者血浆中 PD-L1(+) 外泌体的临床意义。
DOI：
10.1158/1078-0432.ccr-17-2664
发表时间：
2018-02-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Theodoraki MN;Yerneni SS;Hoffmann TK;Gooding WE;Whiteside TL
通讯作者：
Whiteside TL
影响因子：
44.1
作者：
Tang D;Chen X;Kang R;Kroemer G
通讯作者：
Kroemer G
影响因子：
64.8
作者：
Jiang, Le;Kon, Ning;Li, Tongyuan;Wang, Shang-Jui;Su, Tao;Hibshoosh, Hanina;Baer, Richard;Gu, Wei
通讯作者：
Gu, Wei
影响因子：
16
作者：
Crescitelli, Rossella;Lasser, Cecilia;Lotvall, Jan
通讯作者：
Lotvall, Jan