宠物狗可自发发展成弥漫性大B细胞淋巴瘤（DLBCL），并且兽医临床试验已被用于治疗犬DLBCL并为其人类伴侣的临床试验提供了信息。而仍然存在的挑战是选择治疗以改善预后。本研究中的狗是更大临床试验的一部分，该试验评估了多柔比星化学疗法、抗CD20单克隆抗体和三种小分子抑制剂之一（KPT-9274、TAK-981或RV1001）的组合用法。我们假设肿瘤基线处的基因（DEGs）的显著差异表达可以帮助预测哪些狗对每种治疗的响应更好，基于每种药物所靶向的分子途径。为了实现这一目的，我们使用NanoString nCounter犬免疫肿瘤学（IO）面板评估了18只试验狗的淋巴结穿刺物中的基因表达。我们将复发在90天后的狗定义为良好反应者，将在90天之前复发的狗定义为差劲反应者。我们在基线时分析了所有狗，并将差劲反应者与良好反应者进行了比较，发现增加的CCND3与预后差挂钩，而增加的CD36与良好预后相关，与人类相似。治疗组间基因表达差异很小，因此需针对每个治疗组进行单独分析。增加的CREBBP和CDKN1A与KPT-9274相关联，增加的TLR3与TAK-981相关联，增加的PI3Kδ、AKT3和PTEN，以及减少的NRAS与RV1001相关联，与更好的预后相关。通过qPCR验证了所选候选生物标志基因的趋势。我们的研究结果强调了DLBCL的异质性，犬和人类DLBCL之间的相似性和差异性，并最终确定了可能有助于指导犬类化疗免疫治疗选择的生物标志物。版权所有：© 2023 Dittrich等。本文为开放获取文章，根据创作共用许可证，允许在任何媒介上自由使用、分发和复制，只要保留原始作者和出处信息。

Pet dogs develop spontaneous diffuse large B cell lymphoma (DLBCL), and veterinary clinical trials have been employed to treat canine DLBCL and to inform clinical trials for their human companions. A challenge that remains is selection of treatment to improve outcomes. The dogs in this study were part of a larger clinical trial evaluating the use of combinations of doxorubicin chemotherapy, anti-CD20 monoclonal antibody, and one of three small molecule inhibitors: KPT-9274, TAK-981, or RV1001. We hypothesized that significant differential expression of genes (DEGs) in the tumors at baseline could help predict which dogs would respond better to each treatment based on the molecular pathways targeted by each drug. To this end, we evaluated gene expression in lymph node aspirates from 18 trial dogs using the NanoString nCounter Canine Immuno-oncology (IO) Panel. We defined good responders as those who relapsed after 90 days, and poor responders as those who relapsed prior to 90 days. We analyzed all dogs at baseline and compared poor responders to good responders, and found increased CCND3 correlated with poor prognosis and increased CD36 correlated with good prognosis, as is observed in humans. There was minimal DEG overlap between treatment arms, prompting separate analyses for each treatment cohort. Increased CREBBP and CDKN1A for KPT-9274, increased TLR3 for TAK-981, and increased PI3Kδ, AKT3, and PTEN, and decreased NRAS for RV1001 were associated with better prognoses. Trends for selected candidate biomarker genes were confirmed via qPCR. Our findings emphasize the heterogeneity in DLBCL, similarities and differences between canine and human DLBCL, and ultimately identify biomarkers that may help guide the choice of chemoimmunotherapy treatment in dogs.Copyright: © 2023 Dittrich et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.