CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题：Functional expression of aryl hydrocarbon receptor as a potential novel therapeutic target in human multiple myeloma.
Functional expression of aryl hydrocarbon receptor as a potential novel therapeutic target in human multiple myeloma.
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多发性骨髓瘤（MM）的病因仍未充分阐明；不过，流行病学研究提示，接触环境芳香烃与意义未明的单克隆丙种球蛋白病（MGUS）及MM发生之间可能存在联系。环境芳香烃是芳香烃受体（AHR）的外源性配体，而AHR被认为参与癌症生物学。本研究证明，MM细胞系和人原发MM样本中存在具有功能的AHR表达。AHR在推定的MM“干细胞”和MM晚期临床分期中表达，并在功能上参与MM肿瘤细胞表型和增殖。拮抗AHR可直接损害MM细胞存活，并提高MM细胞对免疫介导清除的敏感性。此外，研究结果表明，在未来临床研究中，拮抗AHR可能有效增强其他药物（例如抗CD38抗体）的作用。综合而言，这些数据确认AHR是MM治疗的新靶点。
The etiology of multiple myeloma (MM) remains incompletely understood; however, epidemiologic studies have suggested a possible link between exposure to environmental aromatic hydrocarbons-which serve as exogenous ligands for the aryl hydrocarbon receptor (AHR), which has been implicated in cancer biology-and development of monoclonal gammopathy of undetermined significance (MGUS) and MM.
Herein, we demonstrate the functional expression of AHR in MM cell lines and primary human MM samples. AHR is expressed in putative MM 'stem cells' and advanced clinical stages of MM, and functionally contributes to MM tumor cell phenotype and proliferation. Antagonism of AHR directly impairs MM cell viability and increases MM cell susceptibility to immune-mediated clearance.
Furthermore, our findings indicate that AHR antagonism may represent an effective means to enhance the function of other drugs, such as anti-CD38 antibodies, in future clinical studies. Taken together, these data identify AHR as a novel target for MM therapy.
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