Expression data from transplanted HCmel3 mouse melanomas relapsing to adoptive T-cell therapy in vivo

Adoptive cell therapies (ACT) with cytotoxic T-cell targeting melanocytic antigens can achieve remissions in metastatic melanoma patients, but tumours frequently relapse. To study the underlying mechanisms of resistance we have generated a genetically engineered mouse melanoma model that faithfully recapitulates tumour regression, remission and relapse as seen in patients. HCmel3 mouse melanoma cells were injected into syngneic C57/BL6 (H-2b) mice. We performed transcriptional profiling of control, relapsed and re-transplanted relapsed tumours to characterize the changes in gene expression patterns associated with the respective treament conditions. In addition, we analysed the transcription profile of ACT relapsed melanoma cultures in vitro and the transcriptional response to the inflammatory cytokine Tnf-alpha. The study aimed to identify molecular mechanisms contributing to ACT resistance to optimize therapeutic regimens in the clinic. Total RNA obtained from five biological replicates (rep) of control, relapsed and re-transplanted HCmel3 mouse melanomas in vivo and two biological replicates (rep) of HCmel3 cells, HCmel3-R (relapse) cells and Tnf-alpha treated HCmel3 cells in vitro.

过继性细胞疗法（Adoptive Cell Therapies, ACT）通过靶向黑素细胞抗原的细胞毒性T细胞，可使转移性黑色素瘤患者获得临床缓解，但肿瘤常出现复发。为探究该治疗耐药性的潜在分子机制，本研究构建了一款可忠实重现患者体内肿瘤消退、缓解及复发全过程的基因工程小鼠黑色素瘤模型。将HCmel3小鼠黑色素瘤细胞接种至同基因C57/BL6（H-2b）小鼠体内后，本研究对对照组、复发组及复发性肿瘤再移植组的体内肿瘤样本开展转录组分析，以表征对应处理条件下基因表达模式的变化特征。此外，本研究还分析了体外培养的ACT耐药复发性黑色素瘤细胞的转录组谱，以及该细胞对炎性细胞因子肿瘤坏死因子-α（Tumor Necrosis Factor-alpha, TNF-α）的转录应答反应。本研究旨在明确介导ACT耐药的分子机制，以优化临床治疗方案。本研究获取的总RNA样本来源于：体内对照组、复发组及复发性肿瘤再移植组HCmel3小鼠黑色素瘤的5个生物学重复（rep）样本，以及体外培养的HCmel3野生型细胞、HCmel3-R（复发型）细胞与TNF-α处理的HCmel3细胞的2个生物学重复（rep）样本。