■抑制程序性死亡配体1、程序性死亡1途径已成功用于治疗多种晚期成人癌症。然而,其在小儿骨肉瘤中的应用仍处于起步阶段。在这项研究中,我们研究了程序性死亡配体1和其他检查点分子的表达,以确定作为药物治疗靶点的潜在用途.
■我们将人野生型骨肉瘤细胞与递增浓度的多柔比星孵育以产生多柔比星抗性细胞系。使用Matrigel体外侵袭测定来比较侵袭性。通过Western印迹测定评估比较性程序性死亡配体1表达。免疫肿瘤学检查点蛋白质组用于比较16种其他检查点分子的浓度。卡方检验和Wilcoxon秩和检验用于确定显着差异。
■成功创建了多柔比星抗性细胞系，并且其侵袭性明显高于野生型细胞（0.47vs0.07，P<.001）。在蛋白质印迹分析中，多柔比星抗性但不是野生型细胞表达程序性死亡配体1。多柔比星抗性细胞的T细胞免疫球蛋白-3和分化簇86的水平显著高于野生型细胞，分化簇27、分化簇40、淋巴细胞活化基因-3、分化簇80、死亡程序性配体1、程序性死亡配体2、诱导型T细胞共刺激表达较野生型细胞显著。两系均表达B-和T-淋巴细胞衰减因子，分化簇28，疱疹病毒进入介体，编程死亡1.疱疹病毒进入介体，分化簇40和程序性死亡配体2也存在于两种细胞系的培养基中。
■阿霉素抗性骨肉瘤似乎比非抗性野生型细胞表达更高的程序性死亡配体1。基准检查点分子可能为阐明耐药性和肿瘤转移途径的未来研究提供基础。癌症预后或复发的生物标志物，以及定向药物治疗的未来目标。
UNASSIGNED: Inhibition of the programmed death ligand 1, programmed death 1 pathway has been successfully used for treatment of multiple advanced adult cancers. However, its use in pediatric osteosarcoma is still in its infancy. In this
study, we investigated programmed death ligand 1 and other checkpoint molecules\' expression to determine the potential usefulness as targets for drug therapy.
UNASSIGNED: We incubated human wild-type osteosarcoma cells with incremental concentrations of doxorubicin to create a doxorubicin-resistant cell line. Matrigel in vitro invasion assays were used to compare invasiveness. Comparative programmed death ligand 1 expression was evaluated by Western blot assays. An immuno-oncology checkpoint protein panel was used to compare concentrations of 16 other checkpoint molecules. Chi-square tests and Wilcoxon rank-sum tests were used to determine significant differences.
UNASSIGNED: A doxorubicin-resistant cell line was successfully created and was significantly more invasive than wild-type cells (0.47 vs 0.07, P < .001). On Western blot assay, doxorubicin-resistant but not wild-type cells expressed programmed death ligand 1. Doxorubicin-resistant cells had significantly higher levels of T-cell immunoglobulin-3 and cluster of differentiation 86 and higher cluster of differentiation 27, cluster of differentiation 40, lymphocyte-activation gene-3, cluster of differentiation 80, programmed death ligand 1, programmed death ligand 2, and inducible T-cell costimulatory expression than wild-type cells. Both lines expressed B- and T-lymphocyte attenuator, cluster of differentiation 28, herpesvirus entry mediator, and programmed death 1. Herpesvirus entry mediator, cluster of differentiation 40, and programmed death ligand 2 were also present in the culture media of both cell lines.
UNASSIGNED: Doxorubicin-resistant osteosarcoma seems to express higher programmed death ligand 1 than nonresistant wild-type cells. Benchmarking checkpoint molecules may provide the basis for future studies that elucidate pathways of drug resistance and tumor metastasis, biomarkers for cancer prognosis or recurrence, and future targets for directed drug therapy.
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