Cancer stem cell-derived extracellular vesicles preferentially target MHC-II-macrophages and PD1+ T cells in the tumor microenvironment.
Cancer stem cell-derived extracellular vesicles preferentially target MHC-II-macrophages and PD1+ T cells in the tumor microenvironment.
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DOI：
10.1371/journal.pone.0279400
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发表时间：
2023
期刊：
影响因子：
3.7
通讯作者：
Pucci, Ferdinando
中科院分区：
文献类型：
--
作者：
Gonzalez-Callejo, Patricia;Guo, Zihan;Ziglari, Tahereh;Claudio, Natalie Marcia;Nguyen, Kayla Hoang;Oshimori, Naoki;Seras-Franzoso, Joaquim;Pucci, Ferdinando
免疫疗法是头颈鳞状细胞癌（HNSCC）的一种批准的治疗选择。然而，对于复发性 HNSCC，免疫检查点阻断的缓解率仅为 13%，这凸显了迫切需要更好地了解肿瘤与免疫的相互作用，最终目标是改善患者的预后。 HNSCC 具有较高的局部复发率和治疗耐药性，这可归因于肿瘤内存在癌症干细胞 (CSC)。 CSC 表现出独特的特性，使它们能够避免免疫检测和根除。 CSC 如何与免疫细胞通信以及在 CSC 生态位中优先发现哪些免疫细胞类型仍然是悬而未决的问题。在这里，我们使用遗传方法特异性标记 CSC 衍生的细胞外囊泡 (EV)，并对 CSC 微环境细胞进行分选酶介导的体内邻近标记。我们确定了 EVCSC 选择性靶向且在 CSC 生态位中发现的特定免疫细胞亚群。天然 EVSCC 优先靶向肿瘤微环境中的 MHC-II-巨噬细胞和 PD1+ T 细胞，它们是 CSC 生态位中富集的相同免疫细胞亚群。这些观察结果表明，使用无需体外分离即可追踪 EV 的基因技术是揭示天然 EVSCC 生物学的宝贵工具。
Immunotherapy is an approved treatment option for head and neck squamous cell carcinoma (HNSCC). However, the response rate to immune checkpoint blockade is only 13% for recurrent HNSCC, highlighting the urgent need to better understand tumor-immune interplay, with the ultimate goal of improving patient outcomes. HNSCC present high local recurrence rates and therapy resistance that can be attributed to the presence of cancer stem cells (CSC) within tumors. CSC exhibit singular properties that enable them to avoid immune detection and eradication. How CSC communicate with immune cells and which immune cell types are preferentially found within the CSC niche are still open questions. Here, we used genetic approaches to specifically label CSC-derived extracellular vesicles (EVs) and to perform Sortase-mediated in vivo proximity labeling of CSC niche cells. We identified specific immune cell subsets that were selectively targeted by EVCSC and that were found in the CSC niche. Native EVCSC preferentially targeted MHC-II–macrophages and PD1+ T cells in the tumor microenvironment, which were the same immune cell subsets enriched within the CSC niche. These observations indicate that the use of genetic technologies able to track EVs without in vitro isolation are a valuable tool to unveil the biology of native EVCSC.
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影响因子：
5.6
作者：
Boutilier AJ;Elsawa SF
通讯作者：
Elsawa SF
影响因子：
11.2
作者：
Gomez KE;Wu F;Keysar SB;Morton JJ;Miller B;Chimed TS;Le PN;Nieto C;Chowdhury FN;Tyagi A;Lyons TR;Young CD;Zhou H;Somerset HL;Wang XJ;Jimeno A
通讯作者：
Jimeno A
影响因子：
5.5
作者：
Cai, Jinghua;Qiao, Bin;He, Wei
通讯作者：
He, Wei
影响因子：
4.1
作者：
Hamilton, Nicklas;Claudio, Natalie M.;Pucci, Ferdinando
通讯作者：
Pucci, Ferdinando
肿瘤相关巨噬细胞的细胞和分子起源。
DOI：
10.1126/science.1252510
发表时间：
2014-05-23
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Franklin RA;Liao W;Sarkar A;Kim MV;Bivona MR;Liu K;Pamer EG;Li MO
通讯作者：
Li MO