Department of Oncology and Southwest Cancer Center, Southwest Hospital, The Third Military Medical University (Army Medical University), Chongqing, China.
Department of Oncology and Southwest Cancer Center, Southwest Hospital, The Third Military Medical University (Army Medical University), Chongqing, China.
Exp Cell Res. 2019 Jun 15;379(2):159-165. doi: 10.1016/j.yexcr.2019.03.038. Epub 2019 Apr 2.
IL-10 is commonly regarded as an immunoregulatory cytokine, but accumulating evidence suggests that IL-10 may promote CD8 T cell expansion and proliferation. In this study, tumor infiltrating (TI) and peripheral blood (PB) CD8 T cells were collected from esophageal cancer patients. Interestingly, IL-10 concentration in the tumor microenvironment increased with advancing tumor stage, while TI CD8 T cell-mediated IL-10 production decreased with advancing tumor stage. By flow cytometry, three distinctive subsets, including IL-10IFNγ, IL-10IFNγ, and IL-10IFNγ, could be observed in TI CD8 T cells. The former two subsets were present at much higher frequency in stage I and stage II patients than in stage III patients. IL-10IFNγ TI CD8 T cells presented significantly higher IFNγ and lower PD-1 expression than the IL-10IFNγ TI CD8 T cells. PB CD8 T cells, on the other hand, produced little IL-10 but potent IFNγ upon stimulation. Interestingly, intermediate level of exogenous IL-10 could significantly elevate the expression of IFNγ by PB CD8 T cells, while high level of exogenous IL-10 resulted in reduced expression of IFNγ by PB CD8 T cells. Exogenous IL-10 could not significantly reduce the frequencies of PD-1 PB CD8 T cells, but significantly reduced the MFI of PD-1 in the PB CD8 T cells, especially in stage III patients. Together, this investigation demonstrated that IL-10 enhanced IFNγ expression and suppressed PD-1 expression in PB and TI CD8 T cells; however, the frequency of IL-10-expressing TI CD8 T cells decreased with increasing severity in esophageal cancer.
IL-10 通常被认为是一种免疫调节细胞因子，但越来越多的证据表明，IL-10 可能促进 CD8 T 细胞的扩增和增殖。在这项研究中，我们从食管癌患者中收集了肿瘤浸润（TI）和外周血（PB）CD8 T 细胞。有趣的是，肿瘤微环境中的 IL-10 浓度随着肿瘤分期的进展而增加，而 TI CD8 T 细胞介导的 IL-10 产生则随着肿瘤分期的进展而减少。通过流式细胞术，我们可以在 TI CD8 T 细胞中观察到三种不同的亚群，包括 IL-10IFNγ、IL-10IFNγ和 IL-10IFNγ。前两个亚群在 I 期和 II 期患者中的频率明显高于 III 期患者。IL-10IFNγ TI CD8 T 细胞表现出显著更高的 IFNγ 和更低的 PD-1 表达，而 IL-10IFNγ TI CD8 T 细胞则表现出显著更高的 IFNγ 和更低的 PD-1 表达。相比之下，PB CD8 T 细胞在受到刺激时产生的 IL-10 很少，但产生的 IFNγ 很强。有趣的是，中等水平的外源性 IL-10 可以显著提高 PB CD8 T 细胞 IFNγ 的表达，而高水平的外源性 IL-10 则导致 PB CD8 T 细胞 IFNγ 的表达降低。外源性 IL-10 不能显著降低 PD-1 PB CD8 T 细胞的频率，但能显著降低 PB CD8 T 细胞中 PD-1 的平均荧光强度（MFI），尤其是在 III 期患者中。总之，这项研究表明，IL-10 增强了 PB 和 TI CD8 T 细胞中 IFNγ 的表达，并抑制了 PD-1 的表达；然而，在食管癌中，表达 IL-10 的 TI CD8 T 细胞的频率随着疾病的严重程度而降低。
