Immune activation by combination human lymphokine-activated killer and dendritic cell therapy
Immune activation by combination human lymphokine-activated killer and dendritic cell therapy
复制标题
人淋巴因子激活的杀伤细胞和树突状细胞联合治疗的免疫激活
作者：
E. West;K. Scott;V. Jennings;A. Melcher
背景：癌症的最佳细胞免疫疗法应该理想地利用免疫应答的先天性和适应性臂。巨噬细胞因子激活的杀伤细胞（LAK）可以触发肿瘤靶标的早期先天性杀伤，而长期适应性特异性肿瘤控制需要在抗原呈递细胞如树突状细胞（DC）获得肿瘤相关抗原（TAA）后引发CD 8+细胞毒性淋巴细胞（CTL）。由于DC刺激先天和适应性效应器，使用LAK细胞和DC的组合细胞疗法具有最大化抗肿瘤免疫priming.Methods的潜力：人类临床级LAK细胞和DC之间的相互激活共培养，及其免疫后果，通过细胞表型，细胞因子释放和针对黑色素瘤靶点的先天和适应性细胞毒性的引发来监测。DC和LAK的共培养导致LAK群体内的自然杀伤（NK）细胞的表型活化，这与炎性细胞因子的产生增加和针对肿瘤细胞靶的先天性细胞毒性增强有关。LAK细胞成熟的DC，和LAK细胞和DC的组合，除了黑色素瘤细胞，支持启动特异性抗肿瘤CTL比DCs单独。结论：临床级的LAK细胞/DC代表了一个实用的，有效的组合细胞免疫疗法，刺激先天性和适应性抗肿瘤免疫在癌症患者。
Background:Optimal cellular immunotherapy for cancer should ideally harness both the innate and adaptive arms of the immune response. Lymphokine-activated killer cells (LAKs) can trigger early innate killing of tumour targets, whereas long-term adaptive-specific tumour control requires priming of CD8+ cytotoxic lymphocytes (CTLs) following acquisition of tumour-associated antigens (TAAs) by antigen-presenting cells such as dendritic cells (DCs). As DCs stimulate both innate and adaptive effectors, combination cell therapy using LAKs and DCs has the potential to maximise anti-tumour immune priming.Methods:Reciprocal activation between human clinical grade LAKs and DCs on co-culture, and its immune consequences, was monitored by cell phenotype, cytokine release and priming of both innate and adaptive cytotoxicity against melanoma targets.Results:Co-culture of DCs and LAKs led to phenotypic activation of natural killer (NK) cells within the LAK population, which was associated with increased production of inflammatory cytokines and enhanced innate cytotoxicity against tumour cell targets. The LAKs reciprocally matured DCs, and the combination of LAKs and DCs, on addition of melanoma cells, supported priming of specific anti-tumour CTLs better than DCs alone.Conclusion:Clinical-grade LAKs/DCs represents a practical, effective combination cell immunotherapy for stimulation of both innate and adaptive anti-tumour immunity in cancer patients.
影响因子：
4.5
作者：
Srivastava, S.;Lundqvist, A.;Childs, R. W.
通讯作者：
Childs, R. W.