CD8+ T cell priming by dendritic cell vaccines requires antigen transfer to endogenous antigen presenting cells.
CD8+ T cell priming by dendritic cell vaccines requires antigen transfer to endogenous antigen presenting cells.
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DOI：
10.1371/journal.pone.0011144
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发表时间：
2010-06-16
期刊：
影响因子：
3.7
通讯作者：
Bhardwaj N
中科院分区：
文献类型：
--
作者：
Yewdall AW;Drutman SB;Jinwala F;Bahjat KS;Bhardwaj N
刺激抗肿瘤免疫的免疫策略是用于癌症治疗的有前途的方法。它们成功的主要障碍是肿瘤的免疫抑制微环境，其抑制产生抗肿瘤CD8+ T细胞所必需的内源性树突状细胞（DC）的功能。为了克服这个问题，自体DC离体产生，负载有肿瘤抗原，并在施用于患者之前在这种非抑制性环境中活化。然而，基于DC的疫苗很少诱导肿瘤消退。我们使用小鼠模型研究了这些DC在注射后的命运和功能，以更好地了解它们与宿主免疫系统的相互作用。与先前的假设相反，我们表明DC疫苗在直接引发CD8+ T细胞中的作用微不足道，而是主要用作将抗原转移至内源性抗原呈递细胞的载体，内源性抗原呈递细胞负责随后的T细胞活化。这种对内源性免疫细胞的依赖可能解释了目前DC疫苗治疗癌症的有限成功，并为如何改进这些疗法提供了新的见解。未来的方法应该集中在创造DC疫苗，更有效地直接引发T细胞，或废除肿瘤诱导的内源性DC的抑制。
Immunotherapeutic strategies to stimulate anti-tumor immunity are promising approaches for cancer treatment. A major barrier to their success is the immunosuppressive microenvironment of tumors, which inhibits the functions of endogenous dendritic cells (DCs) that are necessary for the generation of anti-tumor CD8+ T cells. To overcome this problem, autologous DCs are generated ex vivo, loaded with tumor antigens, and activated in this non-suppressive environment before administration to patients. However, DC-based vaccines rarely induce tumor regression. We examined the fate and function of these DCs following their injection using murine models, in order to better understand their interaction with the host immune system. Contrary to previous assumptions, we show that DC vaccines have an insignificant role in directly priming CD8+ T cells, but instead function primarily as vehicles for transferring antigens to endogenous antigen presenting cells, which are responsible for the subsequent activation of T cells. This reliance on endogenous immune cells may explain the limited success of current DC vaccines to treat cancer and offers new insight into how these therapies can be improved. Future approaches should focus on creating DC vaccines that are more effective at directly priming T cells, or abrogating the tumor induced suppression of endogenous DCs.
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影响因子：
32.4
作者：
Jung, S;Unutmaz, D;Lang, RA
通讯作者：
Lang, RA
DOI：
10.1084/jem.20030448
发表时间：
2003-08-18
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
MartIn-Fontecha A;Sebastiani S;Höpken UE;Uguccioni M;Lipp M;Lanzavecchia A;Sallusto F
通讯作者：
Sallusto F
DOI：
10.1084/jem.194.6.769
发表时间：
2001-09-17
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Hawiger D;Inaba K;Dorsett Y;Guo M;Mahnke K;Rivera M;Ravetch JV;Steinman RM;Nussenzweig MC
通讯作者：
Nussenzweig MC
影响因子：
82.9
作者：
Figdor, CG;de Vries, IJM;Melief, CJM
通讯作者：
Melief, CJM
影响因子：
4.4
作者：
Li, M;Davey, GM;Heath, WR
通讯作者：
Heath, WR