Vasir Baldev, Borges Virginia, Wu Zekui, Grosman Daren, Rosenblatt Jacalyn, Irie Masaki, Anderson Kenneth, Kufe Donald, Avigan David
Department of Medical Oncology and Dana-Farber/Harvard Cancer Center, Dana Farber Cancer Institute, Boston, MA 02115, USA.
Br J Haematol. 2005 Jun;129(5):687-700. doi: 10.1111/j.1365-2141.2005.05507.x.
Dendritic cells (DCs) are potent antigen-presenting cells that are uniquely capable of inducing primary immune responses. Although tumour cells may directly inhibit DC maturation, exposure to tumour products may also result in their activation. Fusions of cancer cells and DCs are being explored as cancer vaccines. The effect of tumour cell fusion on DC maturation and their functional characteristics has not been defined. In the present study, immature and mature DC generated from human CD34+ and peripheral blood precursors were fused to multiple myeloma cells in the presence of polyethylene glycol. Fusion of both immature and mature DCs with tumour cells resulted in an activated phenotype. In this regard, fusion cells expressed interleukin-12, a cytokine essential for the induction of T-helper cell type 1 immunity. In contrast to immature DCs, fusion cells also strongly expressed CC-chemokine receptor R7, which is responsible for DC migration to draining lymph nodes. Fusions generated with both immature and mature DCs also potently stimulated T-cell expression of gamma-interferon and cytotoxic T lymphocyte killing of tumour targets. These findings demonstrate that tumour cell fusion induces DC maturation and the development of an activated phenotype necessary for their effectiveness as cancer vaccines.
树突状细胞(DCs)是强大的抗原呈递细胞,具有独特的诱导初始免疫反应的能力。尽管肿瘤细胞可能直接抑制DC成熟,但接触肿瘤产物也可能导致其活化。癌细胞与DC的融合物正作为癌症疫苗进行研究。肿瘤细胞融合对DC成熟及其功能特性的影响尚未明确。在本研究中,在聚乙二醇存在下,将从人CD34 +细胞和外周血前体产生的未成熟和成熟DC与多发性骨髓瘤细胞融合。未成熟和成熟DC与肿瘤细胞的融合均导致活化表型。在这方面,融合细胞表达白细胞介素-12,这是诱导1型辅助性T细胞免疫所必需的细胞因子。与未成熟DC不同,融合细胞还强烈表达CC趋化因子受体R7,其负责DC迁移至引流淋巴结。未成熟和成熟DC产生的融合物也能有效刺激T细胞表达γ-干扰素以及细胞毒性T淋巴细胞对肿瘤靶标的杀伤作用。这些发现表明,肿瘤细胞融合可诱导DC成熟并产生活化表型,这是其作为癌症疫苗发挥效力所必需的。