Phenotyping of lymphoproliferative tumours generated in xenografts of non-small cell lung cancer

Frontiers in Oncology

Oncology

Takahiro Karasaki¹  David R. Pearce²  Charles Swanton²  Ariana Huebner³  Robert E. Hynds⁴  Nicholas McGranahan⁵  Monica Sivakumar⁶  David A. Moore⁶  Teresa Marafioti⁷  Ayse U. Akarca⁷  Venkat Reddy⁸  Roel P. H. De Maeyer⁸  Kavina Shah⁸  Arne N. Akbar⁸  Emily Kostina⁹  Sam M. Janes^1,10 

[1] Cancer Evolution and Genome Stability Laboratory, The Francis Crick Institute, London, United Kingdom;Cancer Research UK (CRUK) Lung Cancer Centre of Excellence, UCL Cancer Institute, University College London, London, United Kingdom;Cancer Evolution and Genome Stability Laboratory, The Francis Crick Institute, London, United Kingdom;Cancer Research UK (CRUK) Lung Cancer Centre of Excellence, UCL Cancer Institute, University College London, London, United Kingdom;Cancer Evolution and Genome Stability Laboratory, The Francis Crick Institute, London, United Kingdom;Cancer Genome Evolution Research Group, UCL Cancer Institute, University College London, London, United Kingdom;Cancer Research UK (CRUK) Lung Cancer Centre of Excellence, UCL Cancer Institute, University College London, London, United Kingdom;Cancer Evolution and Genome Stability Laboratory, The Francis Crick Institute, London, United Kingdom;Epithelial Cell Biology in ENT Research (EpiCENTR) Group, Developmental Biology and Cancer Department, UCL Great Ormond Street Institute of Child Health, University College London, London, United Kingdom;Cancer Research UK (CRUK) Lung Cancer Centre of Excellence, UCL Cancer Institute, University College London, London, United Kingdom;Cancer Genome Evolution Research Group, UCL Cancer Institute, University College London, London, United Kingdom;Cancer Research UK (CRUK) Lung Cancer Centre of Excellence, UCL Cancer Institute, University College London, London, United Kingdom;Department of Cellular Pathology, University College London Hospitals, London, United Kingdom;Department of Cellular Pathology, University College London Hospitals, London, United Kingdom;Division of Medicine, University College London, London, United Kingdom;Epithelial Cell Biology in ENT Research (EpiCENTR) Group, Developmental Biology and Cancer Department, UCL Great Ormond Street Institute of Child Health, University College London, London, United Kingdom;Lungs for Living Research Centre, UCL Respiratory, Division of Medicine, University College London, London, United Kingdom;

关键词: patient-derived xenograft models;    PDX;    pre-clinical modeling;    non-small cell lung cancer;    lymphoproliferation;    Epstein-Barr virus;   

DOI  :  10.3389/fonc.2023.1156743

 received in 2023-02-01, accepted in 2023-05-11,  发布年份 2023

来源: Frontiers

【 摘 要 】

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-scid IL2Rgammanull (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.

【 授权许可】

Unknown   
Copyright © 2023 Pearce, Akarca, De Maeyer, Kostina, Huebner, Sivakumar, Karasaki, Shah, Janes, McGranahan, Reddy, Akbar, Moore, Marafioti, Swanton and Hynds