RESUMEN
Background: Patient-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. Methods: The 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). Results: Lymphoproliferations 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. Discussion: Overall, 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.
RESUMEN
There remains a disparity between the outcomes of male and female prematurely born infants. Our aim was to assess the influence of sex on the requirement for late (> 7 days) postnatal corticosteroid (PNS) treatment and the outcomes following treatment. A retrospective whole population study of infants born at less than 28 weeks of gestation in all neonatal units in England between 2014 and 2018. The impact of exposure to at least five consecutive days of dexamethasone or hydrocortisone on bronchopulmonary dysplasia (BPD) at 36 weeks corrected gestation and survival to discharge from neonatal care was determined. Ten thousand, six hundred and fifty-five infants survived to seven days. Male sex was associated with an increased incidence of BPD (OR 1.41, 95%CI 1.287-1.552, p < 0.001) and death (OR 1.227, 95%CI 1.123-1.452, p < 0.001). Two thousand, three hundred and forty-four infants (22%) received at least one course of PNS at a median of 23 (IQR 15-40) days after birth. Males (23.6%) were more likely to receive PNS than females (20.1%), p < 0.001 and receive repeated courses (mean 1.67 compared to a mean of 1.59 in the females), p = 0.027. Multivariate regression analysis identified no significant differences in the incidence of BPD or death between male and females who received PNS. Conclusions: Males and females had similar outcomes after receiving PNS, but a significantly greater proportion of males met the clinical threshold to receive PNS and were more likely to receive repeated courses which may expose them to a greater risk of adverse long-term outcomes. What is Known: ⢠There remains a difference in outcomes of male and female infants born prematurely. ⢠Prematurely born male infants were more likely to receive postnatal corticosteroids and a greater number of courses but had similar outcomes compared to female infants. What is New: ⢠Postnatal corticosteroids have long-term adverse effects. Such outcomes should be considered when weighing up the risk-benefit ratio of prescribing postnatal corticosteroids, particularly in very prematurely born male infants.
