Institute of Natural Medicine, University of Toyama, Toyama, Japan.
Department of Immunology, Graduate School of Medicine and Pharmaceutical Sciences (Medicine), Toyama, Japan.
Cancer Sci. 2021 Sep;112(9):3484-3490. doi: 10.1111/cas.15050. Epub 2021 Jul 28.
For successful immunotherapy for cancer, it is important to understand the immunological status of tumor antigen-specific CD8 T cells in the tumor microenvironment during tumor progression. In this study, we monitored the behavior of B16OVA-Luc cells in mice immunized with a model tumor antigen ovalbumin (OVA). Using bioluminescence imaging, we identified the time series of OVA-specific CD8 T-cell responses during tumor progression: initial progression, immune control, and the escape phase. As a result of analyzing the status of tumor antigen-specific CD8 cells in those 3 different phases, we found that the expression of NKG2D defines tumor-reacting effector CD8 T cells. NKG2D may control the fate and TOX expression of tumor-reacting CD8 T cells, considering that NKG2D blockade in OVA-vaccinated mice delayed the growth of the B16OVA-Luc2 tumor and increased the presence of tumor-infiltrating OVA-specific CD8 T cells.
为了实现癌症免疫治疗的成功，了解肿瘤进展过程中肿瘤微环境中肿瘤抗原特异性 CD8 T 细胞的免疫状态非常重要。在这项研究中，我们监测了用模型肿瘤抗原卵清蛋白（OVA）免疫的小鼠中 B16OVA-Luc 细胞的行为。通过生物发光成像，我们确定了肿瘤进展过程中 OVA 特异性 CD8 T 细胞反应的时间序列：初始进展、免疫控制和逃逸阶段。通过分析这 3 个不同阶段中肿瘤抗原特异性 CD8 细胞的状态，我们发现 NKG2D 的表达定义了肿瘤反应性效应 CD8 T 细胞。考虑到 NKG2D 阻断可延迟 B16OVA-Luc2 肿瘤的生长并增加肿瘤浸润性 OVA 特异性 CD8 T 细胞的存在，NKG2D 可能控制着肿瘤反应性 CD8 T 细胞的命运和 TOX 表达。
