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首页> 外文期刊>Cytokine >Combination cytokine therapy inhibits tumor growth by generation of tumor-specific T-cell responses in a murine melanoma model.
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Combination cytokine therapy inhibits tumor growth by generation of tumor-specific T-cell responses in a murine melanoma model.

机译:组合细胞因子疗法通过在鼠黑素瘤模型中产生肿瘤特异性T细胞反应来抑制肿瘤生长。

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Various cytokines, including interferon alpha (IFNalpha), tumor necrosis factor alpha (TNFalpha), and granulocyte-macrophage colony-stimulating factor (GM-CSF), have been used as adjuvant therapy for advanced-stage melanoma with some success but with marked toxicity, which appears to be related to higher doses. We investigated the efficacy of IFNalpha, GM-CSF, and TNFalpha in various combinations to induce antitumor and immune responses in a B16F10 murine melanoma model. These studies showed that GM-CSF, IFNalpha, and TNFalpha, when injected together intratumorally, mediated significant inhibition of tumor growth. Tumor regression correlated with local tumor necrosis and significant infiltration of T cells. In addition, this injected intralesional cytokine cocktail also induced lymphadenopathy, with an increase in both CD4(+) and CD8(+) T cells in the draining lymph nodes. Furthermore, tumor-specific CD8(+) T cells were identified from draining lymph nodes. These investigations identify the combined effects of IFNalpha, GM-CSF, and TNFalpha in induction of the adaptive immune response and generation of antigen-specific T-cell reactivity. These results support potential clinical trials of the low-dose cytokine combination as adjuvant therapy for melanoma.
机译:多种细胞因子,包括干扰素α(IFNalpha),肿瘤坏死因子α(TNFalpha)和粒细胞巨噬细胞集落刺激因子(GM-CSF),已被用作晚期黑色素瘤的辅助治疗,虽然取得了一些成功,但毒性明显,这似乎与更高剂量有关。我们研究了IFNalpha,GM-CSF和TNFalpha在各种组合中诱导B16F10小鼠黑素瘤模型的抗肿瘤和免疫反应的功效。这些研究表明,将GM-CSF,IFNα和TNFα肿瘤内注射时,可显着抑制肿瘤生长。肿瘤消退与局部肿瘤坏死和T细胞的显着浸润相关。此外,这种注射的病灶内细胞因子混合物还诱导淋巴结肿大,引流淋巴结中的CD4(+)和CD8(+)T细胞均增加。此外,从引流淋巴结中鉴定出肿瘤特异性CD8(+)T细胞。这些研究确定了IFNalpha,GM-CSF和TNFalpha在诱导适应性免疫应答和抗原特异性T细胞反应性产生中的综合作用。这些结果支持了低剂量细胞因子联合作为黑色素瘤辅助治疗的潜在临床试验。

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