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.
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DOI：
10.1038/s41467-022-31810-6
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发表时间：
2022-07-15
影响因子：
16.6
通讯作者：
Wiita, Arun P.
中科院分区：
文献类型：
--
作者：
Ferguson, Ian D.;Patino-Escobar, Bonell;Tuomivaara, Sami T.;Lin, Yu-Hsiu T.;Nix, Matthew A.;Leung, Kevin K.;Kasap, Corynn;Ramos, Emilio;Vasquez, Wilson Nieves;Talbot, Alexis;Hale, Martina;Naik, Akul;Kishishita, Audrey;Choudhry, Priya;Lopez-Girona, Antonia;Miao, Weili;Wong, Sandy W.;Wolf, Jeffrey L.;Martin, Thomas G.;Shah, Nina;Vandenberg, Scott;Prakash, Sonam;Besse, Lenka;Driessen, Christoph;Posey, Avery D., Jr.;Mullins, R. Dyche;Eyquem, Justin;Wells, James A.;Wiita, Arun P.
骨髓瘤表面蛋白质组（表面组）决定肿瘤与微环境的相互作用，并作为治疗开发的新兴领域。在这里，我们使用糖蛋白捕获蛋白质组学来定义骨髓瘤表面组的基线、耐药性以及对急性药物治疗的反应。我们提供了表面抗原的评分系统，并将 CCR10 确定为这种在恶性浆细胞上广泛表达的疾病的有希望的靶标。我们使用其天然配体 CCL27 设计了针对 CCR10 的原理验证嵌合抗原受体 (CAR) T 细胞。在骨髓瘤模型中，我们鉴定了可作为硼替佐米和来那度胺耐药标记的蛋白质，包括 CD53、CD10、EVI2B 和 CD33。我们发现急性来那度胺治疗通过上调抗原来增加靶向 MUC1 的 CAR-T 细胞的活性。最后，我们开发了一种小型化表面蛋白质组协议，用于以低输入分析原代浆细胞样品。这些方法和数据集可能有助于对骨髓瘤的生物学、治疗和诊断理解。骨髓瘤细胞表面蛋白质组调节浆细胞生物学并确定治疗靶点。在这里，作者对基线和耐药性的骨髓瘤表面组进行了分析，找到了潜在的目标 CCR10，并包括了初级样本分析的简化方法。
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. The myeloma cell surface proteome regulates plasma cell biology and delineates therapy targets. Here, the authors profile the myeloma surfaceome at baseline and in drug resistance, finding the potential target CCR10, and include a streamlined approach to primary sample analysis.
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影响因子：
18.4
作者：
Choudhry P;Galligan D;Wiita AP
通讯作者：
Wiita AP
影响因子：
11.4
作者：
Cooper ML;Choi J;Staser K;Ritchey JK;Devenport JM;Eckardt K;Rettig MP;Wang B;Eissenberg LG;Ghobadi A;Gehrs LN;Prior JL;Achilefu S;Miller CA;Fronick CC;O'Neal J;Gao F;Weinstock DM;Gutierrez A;Fulton RS;DiPersio JF
通讯作者：
DiPersio JF
DOI：
10.1073/pnas.1808790115
发表时间：
2018-11-13
影响因子：
11.1
作者：
Bausch-Fluck D;Goldmann U;Müller S;van Oostrum M;Müller M;Schubert OT;Wollscheid B
通讯作者：
Wollscheid B
影响因子：
12.4
作者：
John, Samuel;Chen, Heyu;Zhang, Cheng Cheng
通讯作者：
Zhang, Cheng Cheng
影响因子：
11.4
作者：
Besse A;Stolze SC;Rasche L;Weinhold N;Morgan GJ;Kraus M;Bader J;Overkleeft HS;Besse L;Driessen C
通讯作者：
Driessen C