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中枢THαβ免疫相关细胞因子:白细胞介素-10对已建立的癌症模型和癌细胞具有强大的抗肿瘤能力。

The Central THαβ Immunity Associated Cytokine: IL-10 Has a Strong Anti-Tumor Ability Toward Established Cancer Models and Toward Cancer Cells .

作者信息

Hu Wan-Chung

机构信息

Genomics Research Center, Academia Sinica, Taipei, Taiwan.

Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, Taiwan.

出版信息

Front Oncol. 2021 Apr 12;11:655554. doi: 10.3389/fonc.2021.655554. eCollection 2021.

Abstract

Immunotherapy is a promising new approach for cancer treatment. In this study, I propose to use the THαβ-mediated immune response for cancer treatment. The THαβ-mediated immune response is activated by IL-10 and IL-15. Thus, I used IL-10 and-15 as therapeutic agents in the 4T1 cell line, which is a mouse cell line of breast cancer, and the NXS2 cell line, which is a mouse cell line of neuroblastoma. Cells from 4T1 and NXS2 were subcutaneously inoculated in wild type BALB/c female mice and AJ mice, respectively, and administered cytokines or an antibody treatment at various dosages. My results showed that IL-10 and IL-15 administration led to reduction in tumor volume and increase in survival. However, traditional TH1 cytokine IFN-γ administration led to increase in tumor volume and decline in survival. Antibody treatment in conjunction with IL-10 was not significantly better than IL-10, due to the expression of GD2 on immune cells. Moreover, an anti-GD2 antibody inhibited the immune cells themselves. Additionally, I found that IL-10 was directly toxic to tumor cells . Thus, I conclude that the THαβ immunological pathway is a good treatment strategy for cancer.

摘要

免疫疗法是一种很有前景的癌症治疗新方法。在本研究中,我提议使用THαβ介导的免疫反应来治疗癌症。THαβ介导的免疫反应由IL-10和IL-15激活。因此,我将IL-10和IL-15作为治疗剂应用于4T1细胞系(一种小鼠乳腺癌细胞系)和NXS2细胞系(一种小鼠神经母细胞瘤细胞系)。分别将来自4T1和NXS2的细胞皮下接种到野生型BALB/c雌性小鼠和AJ小鼠体内,并给予不同剂量的细胞因子或抗体治疗。我的结果表明,给予IL-10和IL-15可导致肿瘤体积减小和生存期延长。然而,给予传统的TH1细胞因子IFN-γ会导致肿瘤体积增大和生存期缩短。由于免疫细胞上GD2的表达,与IL-10联合的抗体治疗并不比IL-10显著更好。此外,抗GD2抗体抑制免疫细胞本身。另外,我发现IL-10对肿瘤细胞有直接毒性。因此,我得出结论,THαβ免疫途径是一种良好的癌症治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f1a8/8072451/ecd81084aa2a/fonc-11-655554-g001.jpg

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