Saito Hiroaki, Dubsky Peter, Dantin Carole, Finn Olivera J, Banchereau Jacques, Palucka A Karolina
Baylor Institute for Immunology Research, Live Oak, Dallas, Texas 75024, USA.
Breast Cancer Res. 2006;8(6):R65. doi: 10.1186/bcr1621.
The ability of dendritic cells (DCs) to take up whole tumor cells and process their antigens for presentation to T cells ('cross-priming') is an important mechanism for induction of tumor specific immunity.
In vitro generated DCs were loaded with killed allogeneic breast cancer cells and offered to autologous naïve CD8+ T cells in 2-week and/or 3-week cultures. CD8+ T cell differentiation was measured by their capacity to secrete effector cytokines (interferon-gamma) and kill breast cancer cells. Specificity was measured using peptides derived from defined breast cancer antigens.
We found that DCs loaded with killed breast cancer cells can prime naïve CD8+ T cells to differentiate into effector cytotoxic T lymphocytes (CTLs). Importantly, these CTLs primed by DCs loaded with killed HLA-A0201- breast cancer cells can kill HLA-A0201+ breast cancer cells. Among the tumor specific CTLs, we found that CTLs specific for HLA-A2 restricted peptides derived from three well known shared breast tumor antigens, namely cyclin B1, MUC-1 and survivin.
This ability of DCs loaded with killed allogeneic breast cancer cells to elicit multiantigen specific immunity supports their use as vaccines in patients with breast cancer.
树突状细胞（DCs）摄取完整肿瘤细胞并处理其抗原以呈递给T细胞（“交叉呈递”）的能力是诱导肿瘤特异性免疫的重要机制。
将体外生成的DCs与灭活的同种异体乳腺癌细胞负载，然后在2周和/或3周培养中提供给自体初始CD8 + T细胞。通过CD8 + T细胞分泌效应细胞因子（干扰素-γ）和杀死乳腺癌细胞的能力来测量其分化情况。使用源自特定乳腺癌抗原的肽来测量特异性。
我们发现，负载灭活乳腺癌细胞的DCs可以使初始CD8 + T细胞分化为效应细胞毒性T淋巴细胞（CTLs）。重要的是，这些由负载灭活HLA-A0201-乳腺癌细胞的DCs引发的CTLs可以杀死HLA-A0201 +乳腺癌细胞。在肿瘤特异性CTLs中，我们发现了对源自三种众所周知的共享乳腺肿瘤抗原（即细胞周期蛋白B1、MUC-1和存活素）的HLA-A2限制性肽具有特异性的CTLs。
负载灭活同种异体乳腺癌细胞的DCs引发多抗原特异性免疫的这种能力支持将其用作乳腺癌患者的疫苗。
