Tumor-infiltrating CD8 T cells are instrumental to antitumor immunity. In this study, we found that a subset of CXCR5-expressing CD8 T cells, termed follicular cytotoxic T (Tfc) cells, potently infiltrated the untreated tumors from non-small cell lung cancer (NSCLC) patients. On average, Tfc cells represented 14% of total tumor-infiltrating CD8 T cells and 6.6% of total tumor-infiltrating lymphocytes. Upon antigenic stimulation, Tfc cells presented significantly higher degranulation and stronger release of proinflammatory cytokines, including IFNg, IL2, and TNF, and the pleiotropic cytokine IL10 than non-Tfc cells. However, the expression of granzyme B and perforin was significantly lower in Tfc cells than in non-Tfc CD8 T cells. B regulatory (Breg) cells could significantly suppress proinflammatory cytokine production in both Tfc cells and non-Tfc CD8 T cells, but in Tfc cells, a lower concentration was required. Moreover, Breg cells could significantly elevate IL10 expression by Tfc cells but could not affect IL-10 expression by non-Tfc CD8 T cells. The neutralization of IL10 significantly reduced the extent of Breg-mediated regulation. Together, this study demonstrated that Tfc cells represented a significant proportion of tumor-infiltrating CD8 T cells in lung carcinoma. These Tfc cells were different from non-Tfc CD8 T cells in terms of cytokine expression and granzyme and perforin release and were more susceptible to Breg-mediated suppression in an IL-10-dependent manner.

中文翻译：

---

滤泡性细胞毒性CD8 T细胞具有较高的细胞因子表达，在非小细胞肺癌中更易受到Breg介导的抑制作用。

肿瘤浸润CD8 T细胞有助于抗肿瘤免疫。在这项研究中，我们发现表达CXCR5的CD8 T细胞的一个子集，称为滤泡细胞毒性T（Tfc）细胞，有效地浸润了来自非小细胞肺癌（NSCLC）患者的未经治疗的肿瘤。平均而言，Tfc细胞占肿瘤总浸润CD8 T细胞的14％和肿瘤总浸润淋巴细胞的6.6％。受到抗原刺激后，与非Tfc细胞相比，Tfc细胞表现出明显更高的脱颗粒度和更强的促炎细胞因子（包括IFNg，IL2和TNF）以及多效性细胞因子IL10释放。但是，Tfc细胞中的颗粒酶B和穿孔素的表达明显低于非Tfc CD8 T细胞。B调节（Breg）细胞可以显着抑制Tfc细胞和非Tfc CD8 T细胞中促炎性细胞因子的产生，但是在Tfc细胞中，需要较低的浓度。此外，Breg细胞可显着提高Tfc细胞的IL10表达，但不会影响非Tfc CD8 T细胞的IL-10表达。IL10的中和作用显着降低了Breg介导的调节程度。总之，这项研究表明，Tfc细胞在肺癌中占肿瘤浸润性CD8 T细胞的很大比例。这些Tfc细胞在细胞因子表达，颗粒酶和穿孔素释放方面与非Tfc CD8 T细胞不同，并且更易受Breg介导的IL-10依赖性抑制的影响。Breg细胞可以显着提高Tfc细胞的IL10表达，但不能影响非Tfc CD8 T细胞的IL-10表达。IL10的中和作用显着降低了Breg介导的调节程度。总之，这项研究表明，Tfc细胞在肺癌中占肿瘤浸润性CD8 T细胞的很大比例。这些Tfc细胞在细胞因子表达，颗粒酶和穿孔素释放方面与非Tfc CD8 T细胞不同，并且更易受Breg介导的IL-10依赖性抑制的影响。Breg细胞可以显着提高Tfc细胞的IL10表达，但不能影响非Tfc CD8 T细胞的IL-10表达。IL10的中和作用显着降低了Breg介导的调节程度。总之，这项研究表明，Tfc细胞在肺癌中占肿瘤浸润性CD8 T细胞的很大比例。这些Tfc细胞在细胞因子表达，颗粒酶和穿孔素释放方面与非Tfc CD8 T细胞不同，并且更易受Breg介导的IL-10依赖性抑制的影响。这项研究表明，Tfc细胞在肺癌中占肿瘤浸润性CD8 T细胞的很大比例。这些Tfc细胞在细胞因子表达，颗粒酶和穿孔素释放方面与非Tfc CD8 T细胞不同，并且更易受Breg介导的IL-10依赖性抑制的影响。这项研究表明，Tfc细胞在肺癌中占肿瘤浸润性CD8 T细胞的很大比例。这些Tfc细胞在细胞因子表达，颗粒酶和穿孔素释放方面与非Tfc CD8 T细胞不同，并且更易受Breg介导的IL-10依赖性抑制的影响。