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首页> 外文期刊>Journal of experimental & clinical cancer research : >Establishment and characterization of patient-derived head and neck cancer models from surgical specimens and endoscopic biopsies
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Establishment and characterization of patient-derived head and neck cancer models from surgical specimens and endoscopic biopsies

机译：从外科标本和内镜活组织检查的患者源头颈部癌模型的建立与表征

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Head and neck squamous cell carcinoma (HNSCC) is heterogeneous in etiology, phenotype and biology. Patient-derived xenografts (PDX) maintain morphology and molecular profiling of the original tumors and have become a standard “Avatar” model for human cancer research. However, restricted availability of tumor samples hindered the widespread use of PDX. Most PDX-projects include only surgical specimens because reliable engraftment from biopsies is missing. Therefore, sample collection is limited and excludes recurrent and metastatic, non-resectable cancer from preclinical models as well as future personalized medicine. This study compares the PDX-take rate, -growth, histopathology, and molecular characteristics of endoscopic specimens with surgical specimens. HNSCC samples (n?=?55) were collected ad hoc, fresh frozen and implanted into NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ mice. Engraftment was successful in both sample types. However, engraftment rate was lower (21?vs. 52%) and growth delayed (11.2 vs. 6.7?weeks) for endoscopic biopsies. Following engraftment, growth kinetic was similar. Comparisons of primary tumors and corresponding PDX models confirmed preservation of histomorphology (HE histology) and molecular profile (Illumina Cancer Hotspot Panel) of the patients’ tumors. Accompanying flow cytometry on primary tumor specimens revealed a heterogeneous tumor microenvironment among individual cases and identified M2-like macrophages as positive predictors for engraftment. Vice versa, a high PD-L1 expression (combined positive score on tumor/immune cells) predicted PDX rejection. Including biopsy samples from locally advanced or metastatic lesions from patients with non-surgical treatment strategies, increases the availability of PDX for basic and translational research. This facilitates (pre-) clinical studies for individual response prediction based on immunological biomarkers.
机译：头部和颈鳞状细胞癌（HNSCC）在病因，表型和生物学中是异质的。患者衍生的异种移植物（PDX）维持原始肿瘤的形态和分子谱，并已成为人体癌症研究的标准“头像”模型。然而，限制肿瘤样品的可用性阻碍了PDX的广泛使用。大多数PDX项目仅包括外科手术标本，因为缺少了从活组织检查的可靠植入。因此，样品收集有限，不包括从临床前模型以及未来个性化药物的复发性和转移性，不可切除的癌症。该研究比较了外科标本的PDX采取率， - Growth，组织病理学和内窥镜标本的分子特征。将Ad Hoc，新鲜冷冻并注入NOD.cg-Prkdcidil2RGTM1WJL / SZJ小鼠。植入在两个样本类型中都是成功的。然而，植入率较低（21？vs.52％）和生长延迟（11.2 vs.6.7？周），用于内窥镜活组织检查。在植入之后，生长动力学相似。原发性肿瘤的比较和相应的PDX模型确认了患者肿瘤的组织（HE组织学）和分子谱（Illumina癌症热点面板）的保存。原发性肿瘤标本上的流式细胞术揭示了个体病例的异质肿瘤微环境，并将M2样巨噬细胞鉴定为植入的阳性预测因子。反之亦然，高PD-L1表达（组合肿瘤/免疫细胞的阳性分数）预测PDX排斥。包括来自非手术治疗策略患者的局部先进或转移性病变的活检样本，增加了PDX的基本和翻译研究的可用性。这促进了基于免疫生物标志物的个体反应预测的临床研究。

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