肿瘤细胞治疗研究
英文原题：The surfaceome of multiple myeloma cells suggests potential immunotherapeutic strategies and protein markers of drug resistance.
The surfaceome of multiple myeloma cells suggests potential immunotherapeutic strategies and protein markers of drug resistance.
骨髓瘤表面蛋白质组（surfaceome）决定了肿瘤与微环境的相互作用，并成为治疗开发的新兴领域。
骨髓瘤细胞表面蛋白组（surfaceome）决定肿瘤与微环境的相互作用，是新兴治疗开发领域。本研究利用糖蛋白捕获蛋白质组学，描绘基线、耐药及急性药物处理后的骨髓瘤表面蛋白组。我们建立了表面抗原评分系统，并发现CCR10是有前景的疾病靶点，广泛表达于恶性浆细胞。我们利用其天然配体CCL27，构建靶向CCR10的概念验证嵌合抗原受体（CAR）T细胞。在骨髓瘤模型中，我们识别出可能作为硼替佐米和来那度胺耐药标志物的蛋白，包括CD53、CD10、EVI2B和CD33。研究发现，急性来那度胺治疗可通过上调抗原，增强靶向MUC1的CAR-T细胞活性。最后，我们开发了一种微型化表面蛋白组流程，可用少量样本分析原代浆细胞。这些方法和数据集有助于加深对骨髓瘤生物学、治疗及诊断的认识。
The myeloma surface proteome (surfaceome) determines tumor interaction with the microenvironment and serves as an emerging arena for therapeutic development. Here, we use glycoprotein capture proteomics to define the myeloma surfaceome at baseline, in drug resistance, and in response to acute drug treatment. We provide a scoring system for surface antigens and identify CCR10 as a promising target in this disease expressed widely on malignant plasma cells. We engineer proof-of-principle chimeric antigen receptor (CAR) T-cells targeting CCR10 using its natural ligand CCL27. In myeloma models we identify proteins that could serve as markers of resistance to bortezomib and lenalidomide, including CD53, CD10, EVI2B, and CD33. We find that acute lenalidomide treatment increases activity of MUC1-targeting CAR-T cells through antigen upregulation. Finally, we develop a miniaturized surface proteomic protocol for profiling primary plasma cell samples with low inputs. These approaches and datasets may contribute to the biological, therapeutic, and diagnostic understanding of myeloma.
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