内源性可溶性受体 sBCMA 和 sTACI：多发性骨髓瘤的生物标志物、免疫调节剂和治疗障碍。
Endogenous soluble receptors sBCMA and sTACI: biomarker, immunoregulator and hurdle for therapy in multiple myeloma.
机构信息
Institute of Clinical Neuroimmunology, University Hospital, LMU Munich, Munich, Germany; Biomedical Center (BMC), Faculty of Medicine, LMU Munich, Martinsried, Germany.
Department of Neurology and Stroke, Hertie Institute for Clinical Brain Research, University of Tübingen, Germany.
出版信息
Curr Opin Immunol. 2021 Aug;71:117-123. doi: 10.1016/j.coi.2021.06.015. Epub 2021 Jul 28.
BAFF and APRIL regulate B cell homeostasis by binding to their three receptors BAFFR, BCMA and TACI. The complexity of this system is further increased by shedding of these three receptors; this reduces signaling due to the display of less surface receptors. Further, soluble forms, sBCMA and sTACI, were detected in body fluids and serve as biomarker in malignancies, autoimmune diseases and immunodeficiencies. sBCMA and sTACI function as decoys blocking BAFF and APRIL. BCMA is a promising therapeutic target in multiple myeloma, but sBCMA may reduce therapeutic activity of CAR T cells, bispecific antibodies, and antibody-drug conjugates. Insights into the biochemical mechanism of shedding of BCMA can be harnessed to improve BCMA-directed therapy by blocking its shedding with a γ-secretase inhibitor.
BAFF 和 APRIL 通过与其三个受体 BAFFR、BCMA 和 TACI 结合来调节 B 细胞内稳态。由于这三个受体的脱落，该系统的复杂性进一步增加，这减少了由于表面受体显示减少而导致的信号转导。此外，还在体液中检测到可溶性形式的 sBCMA 和 sTACI，并作为恶性肿瘤、自身免疫性疾病和免疫缺陷的生物标志物。sBCMA 和 sTACI 作为诱饵发挥作用，阻断 BAFF 和 APRIL。BCMA 是多发性骨髓瘤中很有前途的治疗靶点，但 sBCMA 可能会降低 CAR T 细胞、双特异性抗体和抗体药物偶联物的治疗活性。深入了解 BCMA 脱落的生化机制，可以通过用 γ-分泌酶抑制剂阻断其脱落来改善 BCMA 靶向治疗。
Zotero 插件