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J Leukoc Biol. 2013 Dec;94(6):1141-57. doi: 10.1189/jlb.0613343. Epub 2013 Oct 4.
The identification of an anti-tumor effect displayed by cells of innate immunity has opened new scenarios, not only in the field of allo-HSCT but also for nontransplanted patients with hematological malignancies or solid tumors. Donor-derived NK cells have been shown to contribute to the eradication of malignant cells after allo-HSCT, when recipients lack ligands for their inhibitory receptors. These alloreactive donor NK cells can also kill recipient APCs and CTLs, thus preventing the occurrence of GvHD and graft rejection. The role of activating receptors on the capacity of NK cells to kill leukemia targets has become evident in the last years. The adoptive infusion of ex vivo-activated NK cells has been investigated recently in Phase I/II trials on patients with hematological malignancies and solid tumors, with promising results. γδ T lymphocytes are also able to display anti-tumor activity-this providing the biological rationale for Phase I/II trials in lymphoproliferative disorders and solid tumors. Aminobisphosphonates are clinically available compounds able to boost γδ T cell function. As γδ T cells do not cause GvHD, they could also be transduced with tumor-associated chimeric antigen receptors and safely infused in allo-HSCT recipients. Basic aspects of innate immunity relevant to the field will be covered by a companion review article.
先天免疫细胞显示出的抗肿瘤作用已开辟了新的前景，不仅在同种异体 HSCT 领域，而且在未接受移植的血液系统恶性肿瘤或实体瘤患者中也是如此。已经证明，在同种异体 HSCT 后，当受者缺乏其抑制性受体的配体时，供体来源的 NK 细胞有助于消灭恶性细胞。这些同种反应性供体 NK 细胞还可以杀死受者的 APCs 和 CTLs，从而防止 GvHD 和移植物排斥的发生。近年来，激活受体在 NK 细胞杀伤白血病靶细胞的能力方面的作用变得明显。最近在血液系统恶性肿瘤和实体瘤患者的 I/II 期临床试验中研究了体外激活 NK 细胞的过继输注，结果有希望。γδ T 淋巴细胞也具有抗肿瘤活性——这为淋巴增殖性疾病和实体肿瘤的 I/II 期临床试验提供了生物学依据。氨基双膦酸盐是临床上可用于增强 γδ T 细胞功能的化合物。由于 γδ T 细胞不会引起 GvHD，因此它们也可以被转导带有肿瘤相关嵌合抗原受体，并安全输注到同种异体 HSCT 受者中。一篇相关的综述文章将涵盖与该领域相关的先天免疫的基本方面。
