Gong J, Avigan D, Chen D, Wu Z, Koido S, Kashiwaba M, Kufe D
Dana-Farber Cancer Institute and Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA.
Proc Natl Acad Sci U S A. 2000 Mar 14;97(6):2715-8. doi: 10.1073/pnas.050587197.
We have reported that fusions of murine dendritic cells (DCs) and murine carcinoma cells reverse unresponsiveness to tumor-associated antigens and induce the rejection of established metastases. In the present study, fusions were generated with primary human breast carcinoma cells and autologous DCs. Fusion cells coexpressed tumor-associated antigens and DC-derived costimulatory molecules. The fusion cells also retained the functional potency of DCs and stimulated autologous T cell proliferation. Significantly, the results show that autologous T cells are primed by the fusion cells to induce MHC class I-dependent lysis of autologous breast tumor cells. These findings demonstrate that fusions of human breast cancer cells and DCs activate T cell responses against autologous tumors.
我们曾报道,小鼠树突状细胞(DCs)与小鼠癌细胞的融合可逆转对肿瘤相关抗原的无反应性,并诱导已形成的转移灶被排斥。在本研究中,我们将原发性人乳腺癌细胞与自体DCs进行融合。融合细胞共表达肿瘤相关抗原和DC来源的共刺激分子。融合细胞还保留了DCs的功能效力,并刺激自体T细胞增殖。重要的是,结果表明自体T细胞被融合细胞激活,从而诱导对自体乳腺肿瘤细胞的MHC I类依赖性裂解。这些发现表明,人乳腺癌细胞与DCs的融合可激活针对自体肿瘤的T细胞反应。