Department of Cell, Developmental & Cancer Biology, Oregon Health and Science University, Portland, Oregon, United States of America.
Bionanoplasmonics Group, CIC biomaGUNE, Donostia-San Sebastián, Spain.
PLoS One. 2023 Feb 3;18(2):e0279400. doi: 10.1371/journal.pone.0279400. eCollection 2023.
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.
免疫疗法是头颈部鳞状细胞癌（HNSCC）的一种已批准的治疗选择。然而，对于复发性 HNSCC，免疫检查点阻断的反应率仅为 13%，这突出表明迫切需要更好地了解肿瘤-免疫相互作用，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 表现出使其能够逃避免疫检测和清除的独特特性。CSC 如何与免疫细胞通信以及哪种免疫细胞类型优先存在于 CSC 龛位中，仍然是悬而未决的问题。在这里，我们使用遗传方法专门标记 CSC 衍生的细胞外囊泡（EV），并对 CSC 龛位细胞进行 Sortase 介导的体内邻近标记。我们鉴定了特定的免疫细胞亚群，这些细胞亚群被 EVCSC 选择性靶向，并且存在于 CSC 龛位中。天然 EVCSC 优先靶向肿瘤微环境中的 MHC-II-巨噬细胞和 PD1+T 细胞，这与 CSC 龛位中富集的相同免疫细胞亚群一致。这些观察结果表明，使用能够在不进行体外分离的情况下跟踪 EV 的遗传技术是揭示天然 EVCSC 生物学的有价值的工具。
