The importance of CD4 + T cells in cancer immunotherapy has gained increasing recognition. Particularly, a specific subset of CD4 + T cells coexpressing the T helper type 1 (Th1) and Th17 markers has demonstrated remarkable antitumor potential. However, the underlying mechanisms governing the differentiation of these cells and their subsequent antitumor responses remain incompletely understood. Single-cell RNA sequencing (scRNA-seq) data reanalysis demonstrated the presence of Th 17 1 cells within tumors. Subsequent trajectory analysis found that these Th 17 1 cells are initially primed under Th17 conditions and then converted into IFN-γ-producing cells. Following the in vivo differentiation trajectory of Th 17 1 cells, we successfully established in vitro Th 17 1 cell culture. Transcriptomic profiling has unveiled a substantial resemblance between in vitro-generated Th 17 1 cells and their tumor-infiltrating counterparts. Th 17 1 cells exhibit more potent antitumor responses than Th1 or Th17 cells. Additionally, Th 17 1chimeric antigen receptor T (CAR-T) cells eradicate solid tumors more efficiently. Importantly, Th 17 1 cells display an early exhaustion phenotype while retaining stemness. Mechanistically, Th 17 1 cells migrate faster and accumulate more in tumors in an extracellular matrix protein 1 (ECM1)-dependent manner. Furthermore, we show that IFN-γ up-regulated IRF7 to promote the type I interferon response network and ECM1 expression but decreased the exhaustion status in Th 17 1 cells. Taken together, our findings position Th 17 1 cells as a great candidate for improving targeted immunotherapies in solid malignancies.

中文翻译：

---

通过 IRF7 通过 IFN γ诱导的 I 型干扰素反应网络增强 Th17 来源的 Th1 细胞的抗肿瘤功效


CD4 + T 细胞在癌症免疫治疗中的重要性已得到越来越多的认可。特别是，共表达 T 辅助性 1 型 （Th1） 和 Th17 标志物的 CD4 + T 细胞的特定亚群已显示出显着的抗肿瘤潜力。然而，控制这些细胞分化及其后续抗肿瘤反应的潜在机制仍不完全清楚。单细胞 RNA 测序 （scRNA-seq） 数据再分析表明肿瘤内存在 Th 17 1 细胞。随后的轨迹分析发现，这些 Th 17 1 细胞最初在 Th17 条件下引发，然后转化为产生 IFN γ的细胞。沿着 Th 17 1 细胞的体内分化轨迹，我们成功建立了体外 Th 17 1 细胞培养物。转录组学分析揭示了体外产生的 Th 17 1 细胞与其肿瘤浸润对应物之间的实质性相似之处。Th 17 1 细胞表现出比 Th1 或 Th17 细胞更有效的抗肿瘤反应。此外，Th 17 1 单合抗原受体 T （CAR-T） 细胞可以更有效地根除实体瘤。重要的是，Th 17 1 细胞在保留干性的同时表现出早期耗竭表型。从机制上讲，Th 17 1 细胞迁移得更快，并以细胞外基质蛋白 1 （ECM1） 依赖性方式在肿瘤中积累更多。此外，我们表明 IFN-γ 上调 IRF7 以促进 I 型干扰素反应网络和 ECM1 表达，但降低了 Th 17 1 细胞的耗竭状态。综上所述，我们的研究结果将 Th 17 1 细胞定位为改善实体恶性肿瘤靶向免疫治疗的绝佳候选者。