In vivo imaging of cytotoxic T cell infiltration and elimination of a solid tumor.

In vivo imaging of cytotoxic T cell infiltration and elimination of a solid tumor.
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DOI:
10.1084/jem.20061890
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发表时间:
2007-02-19
期刊:
The Journal of experimental medicine
影响因子:
--
通讯作者:
Amigorena S
Amigorena S
中科院分区:
其他
文献类型:
--
作者:
Boissonnas A;Fetler L;Zeelenberg IS;Hugues S;Amigorena S

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虽然免疫系统进化为对抗感染,但它也可以攻击和摧毁实体瘤。在大多数情况下,肿瘤排斥是由CD8+细胞毒性T淋巴细胞(CTL)引发的,其浸润实体瘤,识别肿瘤抗原并杀死肿瘤细胞。我们在有序的连续切片上使用双光子活体显微镜和免疫荧光的组合来分析CTL对实体瘤的浸润和破坏。我们发现,在胸腺瘤皮下生长的周边,激活的CTL迁移具有高瞬时速度。CTL在与表达其同源抗原的肿瘤细胞密切接触时停滞。在大多数肿瘤细胞死亡的区域,CTL恢复迁移,有时跟随胶原纤维或血管。沿着血管迁移的CTL优先采用伸长的形态。CTL也会深入肿瘤,但仅当肿瘤细胞表达同源CTL抗原时。在不表达同源抗原的肿瘤中,CTL浸润仅限于外周区域,淋巴细胞既不停止移动也不杀死肿瘤细胞。因此,肿瘤细胞的抗原表达决定了肿瘤内的CTL运动性和深度肿瘤浸润。
Although the immune system evolved to fight infections, it may also attack and destroy solid tumors. In most cases, tumor rejection is initiated by CD8+ cytotoxic T lymphocytes (CTLs), which infiltrate solid tumors, recognize tumor antigens, and kill tumor cells. We use a combination of two-photon intravital microscopy and immunofluorescence on ordered sequential sections to analyze the infiltration and destruction of solid tumors by CTLs. We show that in the periphery of a thymoma growing subcutaneously, activated CTLs migrate with high instantaneous velocities. The CTLs arrest in close contact to tumor cells expressing their cognate antigen. In regions where most tumor cells are dead, CTLs resume migration, sometimes following collagen fibers or blood vessels. CTLs migrating along blood vessels preferentially adopt an elongated morphology. CTLs also infiltrate tumors in depth, but only when the tumor cells express the cognate CTL antigen. In tumors that do not express the cognate antigen, CTL infiltration is restricted to peripheral regions, and lymphocytes neither stop moving nor kill tumor cells. Antigen expression by tumor cells therefore determines both CTL motility within the tumor and profound tumor infiltration.
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