Department of Microbiology and Immunology, Otago School of Medical Sciences, University of Otago, Dunedin 9001, New Zealand.
J Immunol. 2014 Mar 1;192(5):2514-21. doi: 10.4049/jimmunol.1202797. Epub 2014 Jan 29.
Increasing evidence suggests that NK cells act to promote effective T cell-based antitumor responses. Using the B16-OVA melanoma model and an optimized Gram-positive bacteria-dendritic cell (DC) vaccination strategy, we determined that in vivo depletion of NK cells at time of tumor challenge abolished the benefit of DC immunotherapy. The contribution of NK cells to DC immunotherapy was dependent on tumor Ag presentation by DC, suggesting that NK cells act as helper cells to prime or reactivate tumor-specific T cells. The absence of NK cells at tumor challenge resulted in greater attenuation of tumor immunity than observed with selective depletion of either CD4 or CD8 T cell subsets. Although successful DC immunotherapy required IFN-γ, perforin expression was dispensable. Closer examination of the role of NK cells as helper cells in enhancing antitumor responses will reveal new strategies for clinical interventions using DC-based immunotherapy.
越来越多的证据表明，NK 细胞有助于促进有效的基于 T 细胞的抗肿瘤反应。我们使用 B16-OVA 黑色素瘤模型和优化的革兰氏阳性细菌-树突状细胞（DC）疫苗接种策略，确定在肿瘤挑战时体内耗尽 NK 细胞会消除 DC 免疫疗法的益处。NK 细胞对 DC 免疫疗法的贡献取决于 DC 对肿瘤 Ag 的呈递，表明 NK 细胞作为辅助细胞来启动或重新激活肿瘤特异性 T 细胞。在肿瘤挑战时缺乏 NK 细胞会导致肿瘤免疫的衰减程度大于选择性耗尽 CD4 或 CD8 T 细胞亚群时观察到的程度。尽管成功的 DC 免疫疗法需要 IFN-γ，但穿孔素的表达是可有可无的。更仔细地研究 NK 细胞作为辅助细胞在增强抗肿瘤反应中的作用将揭示使用基于 DC 的免疫疗法进行临床干预的新策略。
