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首页> 外文期刊>British Journal of Cancer >Alloimmune cells consume interleukin-2 and competitively inhibit the anti-tumour effects of interleukin-2
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Alloimmune cells consume interleukin-2 and competitively inhibit the anti-tumour effects of interleukin-2

机译：同种免疫细胞消耗白细胞介素2并竞争性抑制白细胞介素2的抗肿瘤作用

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Adoptive immunotherapy with lymphokine activated killer (LAK) cells and recombinant interleukin-2 (IL-2) is successful in a variety of tumour models in both the normal and the immunocompromised mouse. We investigated the effects of an immune response to an allogeneic challenge on the metabolism of IL-2. Serum IL-2 levels at different time points after the administration of 20,000 units of IL-2 intraperitoneally were 2-4 fold higher in normal mice than in recently alloimmunized mice. In an intraperitoneal tumour model the alloimmunization of mice with allogeneic P815 tumour cells or splenocytes IP prior to the intraperitoneal inoculation of syngeneic tumour significantly diminished the anti-tumour effects of IL-2 and LAK cell immunotherapy in 7 consecutive experiments. High doses of IL-2 or pretreatment with cyclophosphamide restored the efficacy of IL-2 and LAK cell immunotherapy. From these results we hypothesize that T cells, activated by the allogeneic challenge, consume IL-2 and thus inhibit the effects of IL-2 and LAK cell treatment by competitive inhibition. LAK cell activity with reduced levels of IL-2 cannot be maintained and anti-tumour effects are lost. High doses of IL-2 were shown to overcome the competition for IL-2. Alternatively activated T-cells could be eliminated by pretreatment with cyclophosphamide and anti-tumour effects restored. These results are important in that they provide an alternative explanation as to the mechanism of non-specific cell mediated suppression and may in part explain the failure of some cancer patients to respond to treatment with IL-2 plus LAK immunotherapy.
机译：在正常和免疫功能低下的小鼠的多种肿瘤模型中，淋巴因子激活的杀手（LAK）细胞和重组白介素2（IL-2）采取的过继免疫疗法都是成功的。我们调查了对同种异体挑战的免疫应答对IL-2代谢的影响。腹膜内注射20,000单位IL-2后，不同时间点的血清IL-2水平在正常小鼠中比最近同种免疫的小鼠高2-4倍。在腹膜内肿瘤模型中，在同种肿瘤的腹膜内接种之前，用同种异体P815肿瘤细胞或脾细胞IP进行小鼠同种免疫显着降低了IL-2和LAK细胞免疫疗法的抗肿瘤作用。高剂量的IL-2或用环磷酰胺预处理可恢复IL-2和LAK细胞免疫疗法的功效。根据这些结果，我们假设被同种异体攻击激活的T细胞消耗IL-2，从而通过竞争性抑制作用抑制IL-2和LAK细胞治疗的效果。 IL-2水平降低的LAK细胞活性无法维持，失去抗肿瘤作用。高剂量的IL-2被证明可以克服IL-2的竞争。或者，可以通过用环磷酰胺进行预处理来消除活化的T细胞，并恢复抗肿瘤作用。这些结果很重要，因为它们为非特异性细胞介导的抑制机制提供了另一种解释，并可能部分解释了某些癌症患者对IL-2加LAK免疫疗法治疗无效的原因。

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