DEAD/H (Asp-Glu-Ala-Asp/His) box polypeptide 3, X-linked is an immunogenic target of cancer stem cells
DEAD/H (Asp-Glu-Ala-Asp/His) box polypeptide 3, X-linked is an immunogenic target of cancer stem cells
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DOI：
10.1007/s00262-013-1467-x
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发表时间：
2013-10-01
影响因子：
5.8
通讯作者：
Narita, Ichiei
中科院分区：
文献类型：
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作者：
Koshio, Jun;Kagamu, Hiroshi;Narita, Ichiei
越来越多的证据表明，大多数实体恶性肿瘤由异质性肿瘤细胞组成，相对较小的亚群与干细胞具有相同的生物学特征，可以在化疗和放疗等潜在的致命压力下存活下来。由于这种癌症干细胞（CSC）亚群的存活在复发中起着关键作用，因此必须根除它才能治愈癌症。我们之前报道过，接种具有CSC生物学特征的CD133（+）小鼠黑色素瘤细胞可诱导CSC特异性效应T细胞。它们能够在体内根除CD133（+）肿瘤细胞，从而治愈亲代肿瘤。在本研究中，我们发现DEAD/H （Asp-Glu-Ala-Asp/His）盒多肽3，X-linked （DDX3X）是在CD133（+）肿瘤细胞中优先表达的免疫原性蛋白。接种DDX3X启动特异性T细胞，产生保护性和治疗性抗肿瘤免疫。ddx3x引发的CD4(+) T细胞产生CD133（+）肿瘤特异性IFN γ和IL-17，并介导有效的抗肿瘤治疗效果。DDX3X在多种人类癌细胞中表达，包括肺癌、结肠癌和乳腺癌细胞。这些结果表明，抗ddx3x免疫疗法是一种很有前途的治疗选择，在临床环境中努力根除CSC。
Accumulating evidence suggests that most solid malignancies consist of heterogeneous tumor cells and that a relatively small subpopulation, which shares biological features with stem cells, survives through potentially lethal stresses such as chemotherapy and radiation treatment. Since the survival of this subpopulation of cancer stem cells (CSC) plays a critical role in recurrence, it must be eradicated in order to cure cancer. We previously reported that vaccination with CD133(+) murine melanoma cells exhibiting biological CSC features induced CSC-specific effector T cells. These were capable of eradicating CD133(+) tumor cells in vivo, thereby curing the parental tumor. In the current study, we indicated that DEAD/H (Asp-Glu-Ala-Asp/His) box polypeptide 3, X-linked (DDX3X) is an immunogenic protein preferentially expressed in CD133(+) tumor cells. Vaccination with DDX3X primed specific T cells, resulting in protective and therapeutic antitumor immunity. The DDX3X-primed CD4(+) T cells produced CD133(+) tumor-specific IFN gamma and IL-17 and mediated potent antitumor therapeutic efficacy. DDX3X is expressed in various human cancer cells, including lung, colon, and breast cancer cells. These results suggest that anti-DDX3X immunotherapy is a promising treatment option in efforts to eradicate CSC in the clinical setting.