Phenotyping of lymphoproliferative tumours generated in xenografts of non-small cell lung cancer
Phenotyping of lymphoproliferative tumours generated in xenografts of non-small cell lung cancer
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非小细胞肺癌异种移植物中产生的淋巴增殖性肿瘤的表型分析
DOI：
10.1101/2023.01.24.520089
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Pearce D
中科院分区：
文献类型：
--
作者：
Pearce D
PDX模型涉及免疫缺陷小鼠体内肿瘤组织的植入，是一种重要的临床前肿瘤学研究方法。非小细胞肺癌(NSCLC)PDX模型在NOD-SCIL2RGammanull(NSG)小鼠中的一个局限性是初始植入的一部分来自淋巴细胞，而不是肿瘤来源。为了展示这里的组织学数据，我们开发了一种基于PYTHON的工具，用于从整个幻灯片图像文件生成患者级别的病理概述图；PATH概述可在GitHub上获得，(https://github.com/EpiCENTR-Lab/PATHOverview).ResultsLymphoproliferations发生在17.8%的肺腺癌和10%的肺鳞癌移植手术中，尽管这些患者之前或之后都没有淋巴增生性疾病的临床病史。淋巴增殖主要是人类CD20+B细胞，具有移植后弥漫性大B细胞淋巴瘤的免疫表型，具有浆细胞特征。所有淋巴组织均表达Epstein-Barr编码的RNA(EBER)。对三个肿瘤中免疫球蛋白轻链基因重排的分析表明，每个肿瘤都有独立的克隆性起源。讨论，这些数据表明，在原发非小细胞肺癌肿瘤中存在具有淋巴增殖潜力的B细胞克隆，这些克隆正在持续的免疫监测中。由于这些细胞可以在移植到NSG小鼠体内后扩增，我们的数据突出了质量控制措施的价值，以识别异种移植管道内的淋巴增殖，并支持在异种移植建立管道的早期阶段纳入将淋巴增殖降至最低的策略。
BackgroundPatient-derived xenograft (PDX) models involve the engraftment of tumour tissue in immunocompromised mice and represent an important pre-clinical oncology research method. A limitation of non-small cell lung cancer (NSCLC) PDX model derivation in NOD-scidIL2Rgammanull(NSG) mice is that a subset of initial engraftments are of lymphocytic, rather than tumour origin.MethodsThe immunophenotype of lymphoproliferations arising in the lung TRACERx PDX pipeline were characterised. To present the histology data herein, we developed a Python-based tool for generating patient-level pathology overview figures from whole-slide image files; PATHOverview is available on GitHub (https://github.com/EpiCENTR-Lab/PATHOverview).ResultsLymphoproliferations occurred in 17.8% of lung adenocarcinoma and 10% of lung squamous cell carcinoma transplantations, despite none of these patients having a prior or subsequent clinical history of lymphoproliferative disease. Lymphoproliferations were predominantly human CD20+ B cells and had the immunophenotype expected for post-transplantation diffuse large B cell lymphoma with plasma cell features. All lymphoproliferations expressed Epstein-Barr-encoded RNAs (EBER). Analysis of immunoglobulin light chain gene rearrangements in three tumours where multiple tumour regions had resulted in lymphoproliferations suggested that each had independent clonal origins.DiscussionOverall, these data suggest that B cell clones with lymphoproliferative potential are present within primary NSCLC tumours, and that these are under continuous immune surveillance. Since these cells can be expanded following transplantation into NSG mice, our data highlight the value of quality control measures to identify lymphoproliferations within xenograft pipelines and support the incorporation of strategies to minimise lymphoproliferations during the early stages of xenograft establishment pipelines.
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影响因子：
11.4
作者：
Langerak, A. W.;Molina, T. J.;Van Krieken, J. H. J. M.
通讯作者：
Van Krieken, J. H. J. M.
DOI：
10.1073/pnas.78.2.805
发表时间：
1981-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
LERNER, MR;ANDREWS, NC;STEITZ, JA
通讯作者：
STEITZ, JA
Kappa+ lambda+双受体B细胞存在于人的外围曲目中。
影响因子：
15.3
作者：
Giachino, Claudia;Padovan, Elisabetta;Lanzavecchia, Antonio
通讯作者：
Lanzavecchia, Antonio
影响因子：
5.3
作者：
Kang, Han Na;Choi, Jae Woo;Kim, Hye Ryun
通讯作者：
Kim, Hye Ryun
影响因子：
6.4
作者：
Wang, Dennis;Nhu-An Pham;Tsao, Ming-Sound
通讯作者：
Tsao, Ming-Sound