Transferable anticancer innate immunity in spontaneous regression/complete resistance mice
Transferable anticancer innate immunity in spontaneous regression/complete resistance mice
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DOI：
10.1073/pnas.0602382103
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发表时间：
2006-05-16
影响因子：
11.1
通讯作者：
Cui, Zheng
中科院分区：
文献类型：
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作者：
Hicks, Amy M.;Riedlinger, Gregory;Cui, Zheng
自发消退/完全抗性（SR/CR）小鼠抵抗非常高剂量的癌细胞，即使在低剂量下，这些癌细胞对WT小鼠也是致命的。在这项研究中，我们表明，这种阻力是介导的白细胞，主要是先天免疫，在原发性和反复的挑战快速浸润。随后通过快速细胞溶解破坏癌细胞需要与浸润的自然杀伤细胞、嗜中性粒细胞和巨噬细胞一起形成红细胞。来自SR/CR小鼠的高度纯化的自然杀伤细胞、巨噬细胞和中性粒细胞在体外独立地杀死癌细胞。每个效应细胞亚群的独立杀伤活性与以下观察结果一致，即通过消耗总浸润白细胞而不是仅消耗一个或两个白细胞亚群来消除抗性。抗性可通过SR/CR脾细胞、骨髓细胞或富集的腹腔巨噬细胞完全转移至WT受体小鼠，用于预防随后的癌症攻击或根除远处已建立的恶性肿瘤。
Spontaneous regression/complete resistance (SR/CR) mice resist very high doses of cancer cells that are lethal to WT mice even at low doses. In this study, we show that this resistance is mediated by rapid infiltration of leukocytes, mostly of innate immunity, in both primary and repeated challenges. Formation of rosettes with infiltrating natural killer cells, neutrophils, and macrophages was required for the subsequent destruction of cancer cells through rapid cytolysis. Highly purified natural killer cells, macrophages, and neutrophils from the SR/CR mice independently killed cancer cells in vitro. The independent killing activity by each subset of effector cells is consistent with the observation that the resistance was abolished by depleting total infiltrating leukocytes but not by depleting only one or two subsets of leukocytes. The resistance was completely transferable to WT recipient mice through SR/CR splenocytes, bone marrow cells, or enriched peritoneal macrophages, either for prevention against subsequent cancer challenges or eradication of established malignancy at distant sites.