Loss of tumorigenicity and increased immunogenicity induced by interleukin-10 gene transfer in B16 melanoma cells
Loss of tumorigenicity and increased immunogenicity induced by interleukin-10 gene transfer in B16 melanoma cells
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DOI：
10.1089/hum.1996.7.1-23
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发表时间：
1996-01-01
影响因子：
4.2
通讯作者：
Velu, T
中科院分区：
文献类型：
--
作者：
Gerard, CM;Bruyns, C;Velu, T
由于白细胞介素-10（IL-10）具有有效的免疫抑制和抗炎特性，并且由某些癌症产生，因此我们假设其产生可能通过抑制足够的抗肿瘤免疫应答在致癌作用中发挥作用。为了检验这一假设，产生了含有IL-10 cDNA的逆转录病毒载体，并将其用于感染皮下注射到同基因小鼠中的B16 F1黑素瘤细胞。令人惊讶的是，IL-10基因转移导致与分泌的IL-10的量成比例的致瘤性的丧失。组织学分析显示这些肿瘤细胞的大面积坏死，伴有多形性炎性细胞的浸润。同时植入的亲本细胞只有在与IL 10产生细胞混合时才能降低致瘤性，但在对侧注射时则不然，这表明它们的根除主要是由局部现象介导的。宿主T淋巴细胞和自然杀伤（NK）细胞参与了这种根除，因为产生IL-10的细胞在裸鼠和CD 8（+）或NK耗竭的小鼠中生长。最后，注射IL-10分泌细胞的小鼠产生了抗肿瘤全身免疫应答，能够保护它们免受随后的亲代tells攻击。这些结果表明，在某些情况下，IL 10可能具有体内免疫刺激和促炎特性，需要在其治疗开发中加以考虑。
Because interleukin-10 (IL-10) has potent immunosuppressive and anti-inflammatory properties and is produced by some cancers, we hypothesized that its production might play a role in carcinogenesis by inhibiting adequate antitumoral immune responses. To test this hypothesis, retroviral vectors containing the IL-10 cDNA were generated and used to infect B16F1 melanoma cells that were injected subcutaneously in syngeneic mice. Surprisingly, IL-10 gene transfer resulted in a loss of tumorigenicity that was proportional to the amount of IL-10 secreted. Histological analysis showed massive area of necrosis of these tumor cells, with infiltration of polymorphic inflammatory cells. Parental cells simultaneously implanted had decreased tumorigenicity only when mixed with IL10-producing cells, but not when injected contralaterally, suggesting that their eradication is mediated mostly by a local phenomenon. Host T lymphocytes and natural killer (NK) cells were involved in this eradication because IL-10-producing cells grew in nude mice and in CD8(+) or NK-depleted mice. Finally, mice injected with IL-10-secreting cells developed an antitumoral systemic immune response able to protect them against a subsequent challenge with parental tells. These results demonstrate that, in some settings, IL10 may have in vivo immunostimulating and proinflammatory properties that need to be considered in its therapeutic development.