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首页 » 免疫学 » Haematologica:激活免疫细胞提高疫苗治疗白血病患者的功效

Haematologica:激活免疫细胞提高疫苗治疗白血病患者的功效

来源:生物谷 2012-11-22 10:15

2012年11月21日 讯 /生物谷BIOON/ --近日,Malaghan医学研究所进行一项新研究发现,促进一种罕见免疫细胞的活性,可能使得慢性淋巴细胞白血病患者所接种疫苗能更有效地治疗癌症。

慢性淋巴细胞白血病是新西兰最常见的血液癌症。慢性淋巴细胞白血病随着年龄的增加患病率也增加,在70岁以上的人中,每400人中就有一位是慢性淋巴细胞白血病患者。血液学家Robert Weinkove博士说,骨髓移植是唯一的治疗慢性淋巴细胞白血病的方式。骨髓移植发挥治疗作用的原因是新的(供体)免疫系统能识别白血病细胞,并摧毁了他们。

但骨髓移植也不是没有自己的问题,不是所有的患者都能找到一个供体,患者很容易在数月甚至数年之后发生感染,以及骨髓移植治疗本身也是有毒的。因此有必要确定更有针对性的,低风险的免疫疗法,研究人员专注于一种罕见的免疫细胞 iNKT细胞,Weinkove博士说:以前的研究已经表明,iNKT细胞可以激活α-半乳糖(α-神经酰胺)。

2008年至2011年间,博士Weinkove从40 慢性淋巴细胞白血病患者和30例年纪相仿的健康志愿者中收集血液样本。然后,他进行了一系列的实验室测试,以比较这些人的iNKT细胞的数量和功能。这项研究最近已发表在Haematologica杂志上。博士说:我们可以从检测和分离慢性淋巴细胞白血病患者体内的iNKT细胞,而这些细胞是能够响应α-神经酰胺的。

这是很重要的,因为它表明iNKT细胞在这些患者中保持了一定的功能,通过针对这些细胞开展治疗如用α-神经酰胺刺激可能提高这类免疫细胞的活性,促动他们抗肿瘤免疫反应的能力。(生物谷:Bioon.com)

Functional invariant natural killer T cell and CD1d axis in chronic lymphocytic leukemia: implications for immunotherapy

Robert Weinkove1,*, Collin R. Brooks2, John M. Carter3, Ian F. Hermans1 and Franca Ronchese1

Background Invariant natural killer T cells recognise glycolipid antigens such as α- galactosylceramide presented by CD1d. In preclinical models of B cell malignancies, α-galactosylceramide is an adjuvant to tumor vaccination, enhancing tumor-specific T cell responses and prolonging survival. However, numerical and functional invariant natural killer T cell defects exist in patients with some cancers. We aimed to assess this axis in patients with chronic lymphocytic leukemia. Design and methods Circulating invariant natural killer T cell numbers and antigen presenting cell CD1d expression were measured in patients with chronic lymphocytic leukemia and age-matched controls. Cytokine profile and in vitro proliferative capacity were determined. Patient- and control-derived invariant natural killer T cell lines were generated and characterized, and allogeneic and autologous responses to α-galactosylceramide-treated leukemia cells were assessed. Results Absolute numbers and phenotype of invariant natural killer T cells were normal in untreated chronic lymphocytic leukemia, and cytokine profile and proliferative capacity were intact. Chemotherapy-treated patients had reduced invariant natural killer T and myeloid dendritic cell numbers, but α- galactosylceramide-induced proliferation was preserved. Invariant natural killer T cell lines from patients lysed CD1d-expressing targets. Irradiated α-galactosylceramide- treated leukemic cells elicited allogeneic and autologous invariant natural killer T cell proliferation, and α-galactosylceramide treatment led to increased proliferation of conventional T cells in response to tumor. Conclusions The invariant natural killer T cell and CD1d axis is fundamentally intact in patients with early-stage chronic lymphocytic leukemia, and despite reduced circulating numbers, function is retained in fludarabine-treated patients. Immunotherapies exploiting the adjuvant effect of α-galactosylceramide may be feasible. 

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