Mohty Mohamad, Isnardon Daniel, Charbonnier Aude, Lafage-Pochitaloff Marina, Merlin Michele, Sainty Danielle, Olive Daniel, Gaugler Béatrice
Laboratoire d'Immunologie des Tumeurs, Institut Paoli-Calmettes, Université de la Méditerranée, 232 Boulevard Ste Marguerite, 13273 Marseille Cedex, France.
Int Immunol. 2002 Jul;14(7):741-50. doi: 10.1093/intimm/dxf036.
Dendritic cells (DC) are a group of potent antigen-presenting cells (APC) specialized for initiating T cell immune responses. They originate from the bone marrow and upon stimulation with bacterial products, cytokines or CD40 ligation they acquire the ability to migrate to the secondary lymphoid organs. In vitro DC can be generated from human CD34(+) bone marrow cells and CD14(+) peripheral blood monocytes after culture with different cytokine combinations. Since most leukemic cells and tumors in general are devoid of APC capacities, various strategies have been used to increase their recognition and confer the capacity of antigen presentation on them. Because of our interest in the design of vaccine immunotherapy protocols for the adjuvant treatment of patients with lymphoid malignancies (LM), we chose to explore the capacity of human acute lymphoblastic leukemia, chronic lymphocytic leukemia and plasma cell leukemia to differentiate into cells with APC and DC features. Our results among a sample of 10 patients demonstrate that such approach is feasible. Leukemic cells could be induced in the presence of IL-4 and CD40L to exhibit a DC morphology with a phenotype of mature DC-like cells. They could also induce a potent proliferative response in naive CD4(+) T cells. In addition, they expressed chemokine receptor CCR7 and CD62L, and could drive T cells towards a T(h)1 response with secretion of IFN-gamma. Our strategy leading to increased LM cell immunogenicity may have potential clinical applications and LM appear to be attracting candidates for adjuvant vaccination and adoptive immunotherapy.
树突状细胞（DC）是一组强大的抗原呈递细胞（APC），专门用于启动T细胞免疫反应。它们起源于骨髓，在受到细菌产物、细胞因子或CD40连接刺激后，获得迁移至二级淋巴器官的能力。体外培养时，通过不同细胞因子组合培养，可从人CD34(+)骨髓细胞和CD14(+)外周血单核细胞生成DC。由于大多数白血病细胞和肿瘤总体上缺乏APC能力，人们采用了各种策略来增强它们的识别能力并赋予其抗原呈递能力。鉴于我们对设计用于辅助治疗淋巴系统恶性肿瘤（LM）患者的疫苗免疫治疗方案感兴趣，我们选择探索人类急性淋巴细胞白血病、慢性淋巴细胞白血病和浆细胞白血病分化为具有APC和DC特征细胞的能力。我们在10例患者样本中的结果表明，这种方法是可行的。在IL-4和CD40L存在的情况下，白血病细胞可被诱导呈现出具有成熟DC样细胞表型的DC形态。它们还能在幼稚CD4(+) T细胞中诱导强烈的增殖反应。此外，它们表达趋化因子受体CCR7和CD62L，并可通过分泌IFN-γ促使T细胞朝着T(h)1反应方向发展。我们提高LM细胞免疫原性的策略可能具有潜在的临床应用价值，并且LM似乎正吸引着辅助疫苗接种和过继免疫治疗的候选对象。
