Tumor-infiltrating dendritic cells are potent antigen-presenting cells able to activate T cells and mediate tumor rejection
Tumor-infiltrating dendritic cells are potent antigen-presenting cells able to activate T cells and mediate tumor rejection
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DOI：
10.4049/jimmunol.176.1.61
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发表时间：
2006-01-01
影响因子：
4.4
通讯作者：
French, LE
中科院分区：
文献类型：
--
作者：
Preynat-Seauve, O;Schuler, P;French, LE
树突状细胞（DC）是免疫反应的有效诱导剂。DC已被证明浸润肿瘤，但对这些自然发生的肿瘤浸润DC （TIDC）的功能状态知之甚少。本研究详细研究了几种小鼠黑色素瘤中TIDC的状态和功能。CD11c(+)/MHC II+细胞与DC表型一致，在所有研究的可移植或自发黑色素瘤中均发现。这些TIDC本质上主要是髓细胞(CD11c(+)/CD8 α (-)/B220(-))，少量浆细胞(CD11c（+)/B220(+)）。TIDC具有中等成熟表型，具有一定的共刺激分子表达和颗粒吸收能力。体外培养过夜后，TIDC显著上调共刺激分子的表达，并增加IL-12的产生。重要的是，这种体外成熟的TIDC与OVA脉冲能够迁移到淋巴结，激活。初始ova特异性CD4（+）和CD8(+) T细胞，并赋予保护免受表达ova的肿瘤细胞的攻击。总之，黑素瘤被功能性DC浸润，可以作为完全胜任的APC。这些APC有可能被操纵，因此可能代表癌症免疫治疗的一个有希望的目标。
Dendritic cells (DC) are potent inducers of immune responses. DC have been shown to infiltrate tumors, but very little is known about the functional status of these naturally occurring tumor-infiltrating DC (TIDC). In this study, the status and function of TIDC from several types of mouse melanoma were investigated in detail. CD11c(+)/MHC II+ cells, consistent with a DC phenotype, were found in all of transplantable or spontaneous melanomas studied. These TIDC were predominantly myeloid (CD11c(+)/CD8 alpha(-)/B220(-)) in nature with small numbers of plasmacytoid (CD11c(+)/B220(+)). TIDC had an intermediate maturation phenotype with some expression of costimulatory molecules and the capacity to take up particles. Upon culture overnight ex vivo, the TIDC markedly up-regulated the expression of costimulatory molecules and also increased IL-12 production. Importantly, such ex vivo-matured TIDC pulsed with OVA were able to migrate to lymph nodes, to activate. naive OVA-specific CD4(+) and CD8(+) T cells, and to confer protection against a challenge with OVA-expressing tumor cells. In conclusion, melanomas are infiltrated by functional DC that can act as fully competent APC. These APC have the potential to be manipulated and may therefore represent a promising target for cancer immunotherapy.