RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
肿瘤微环境中对 rMV-SLAMblind 癌症病毒治疗引发的免疫反应
英文原题：Immune response elicited in the tumor microenvironment upon rMV-SLAMblind cancer virotherapy.
查看英文原题
Immune response elicited in the tumor microenvironment upon rMV-SLAMblind cancer virotherapy.
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中文摘要
溶瘤病毒治疗是一种有前景的癌症治疗方法。我们之前建立了一种重组麻疹病毒（rMV-SLAMblind），靶向表达 NECTIN4 的癌细胞，并在免疫缺陷小鼠的异种移植模型中证明了其抗肿瘤效果。
在本研究中，为了探究 rMV-SLAMblind 治疗后的免疫反应，我们通过将 NECTIN4 基因导入小鼠癌细胞系，建立了一种具有免疫活性的癌症小鼠模型。表达 NECTIN4 的小鼠癌细胞在体外被 rMV-SLAMblind 成功杀伤。移植表达 NECTIN4 的肿瘤细胞后，rMV-SLAMblind 在具有免疫活性的小鼠中显著抑制了肿瘤生长。
因此，这种具有免疫活性的小鼠癌症模型可以成为研究 rMV-SLAMblind 治疗对免疫反应影响的有力工具。利用该模型，我们发现 rMV-SLAMblind 在肿瘤微环境中引起了NK 细胞、1 型辅助 T 细胞和肿瘤特异性 CD8 + T 细胞反应的显著激活。免疫细胞清除研究揭示，CD8 + 细胞在 rMV-SLAMblind 的治疗效果中尤其发挥了重要作用。
因此，rMV-SLAMblind 不仅通过直接杀伤肿瘤细胞发挥治疗效果，还通过有效诱导抗肿瘤免疫间接发挥作用。
展开英文摘要原文
Oncolytic virotherapy is a promising therapy for cancer. We previously established a recombinant measles virus (rMV-SLAMblind) that targets NECTIN4-expressing cancer cells and demonstrated its antitumor effects using a xenograft model in an immunodeficient mouse.
In the current study, to investigate the immune response after rMV-SLAMblind therapy, we developed an immunocompetent cancer mouse model by introducing the NECTIN4 gene into mouse cancer cell lines. NECTIN4-expressing mouse cancer cells were successfully killed by rMV-SLAMblind in vitro. After transplantation of the NECTIN4-expressing tumor cells, rMV-SLAMblind significantly suppressed tumor growth in immunocompetent mice.
Thus, this immunocompetent mouse cancer model could be a powerful tool in which to study the effect of rMV-SLAMblind therapy on the immune response. Using this model we found that rMV-SLAMblind elicited significant activation of natural killer cells, type 1 helper T cells and the tumor-specific CD8 + T-cell response in the tumor microenvironment. Immune cell depletion study revealed that CD8 + cells particularly played significant roles in the therapeutic efficacy of rMV-SLAMblind.
Thus, rMV-SLAMblind exerts a therapeutic effect, not only directly by tumor cell killing, but also indirectly by efficient induction of antitumor immunity.
论文信息
- 作者
- Moritoh K、Shoji K、Amagai Y、Fujiyuki T、Sato H、Yoneda M、Kai C
- 单位
- Laboratory Animal Research Center, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.Japan
- 期刊
- Cancer science2023 May
- 原文标识
- PubMed 36715555 · DOI 10.1111/cas.15740
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