Single-cell profiling of tumor-infiltrating TCF1/TCF7+ T cells reveals a T lymphocyte subset associated with tertiary lymphoid structures/organs and a superior prognosis in oral cancer
Single-cell profiling of tumor-infiltrating TCF1/TCF7+ T cells reveals a T lymphocyte subset associated with tertiary lymphoid structures/organs and a superior prognosis in oral cancer
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肿瘤浸润 TCF1/TCF7 T 细胞的单细胞分析揭示了与三级淋巴结构/器官相关的 T 淋巴细胞亚群以及口腔癌的良好预后
DOI：
10.1016/j.oraloncology.2021.105348
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发表时间：
2021-05-25
期刊：
影响因子：
4.8
通讯作者：
Li, Jinsong
中科院分区：
文献类型：
--
作者：
Peng, Yu;Xiao, Liping;Li, Jinsong
目的：尽管口腔鳞状细胞癌（OSCC）的治疗取得了实质性进展，但临床结果仍不令人满意。肿瘤浸润淋巴细胞（TIL）是患者的重要预后因素，并且是异质性的。有研究表明，TCF 1/TCF 7 + T细胞和三级淋巴结构/器官（TLS）在肿瘤免疫中起重要作用。但它们如何影响肿瘤免疫以及是否与口腔鳞癌的预后有关尚未见详细报道。材料和方法：我们分离OSCC细胞并进行单细胞RNA测序（scRNA-seq）。采用免疫组化方法分析TLSs与预后的关系。采用多重免疫组化（MIHC）、流式细胞术（FCM）和空间分析等方法验证TCF 1/TCF 7 + T细胞的特征。通过多因素分析和Scenic软件确定TCF 1/TCF 7 + T细胞亚群的预后意义和上游调控网络。结果：TCF 1/TCF 7 + T细胞亚群、TLSs与预后密切相关。结果表明，TCF 1/TCF 7 + T细胞表达高水平的TLS相关基因和低水平的免疫检查点分子。最后，我们发现TCF 1/TCF 7 + T细胞与良好的结局显著相关。结论：TCF 1/TCF 7 + T细胞可作为一个新的治疗靶点，调节OSCC的免疫反应，并有望成为一个新的预后指标。
Objectives: Despite substantial advances in treatment, clinical outcomes for oral squamous cell carcinoma (OSCC) remain unsatisfactory. Tumor-infiltrating lymphocytes (TILs) are an important prognostic factor for patients and are heterogeneous. Some studies have suggested that TCF1/TCF7+ T cells and tertiary lymphatic structure/organ (TLS) play an important role in tumor immunity. However, how they affect tumor immunity and whether they are related to prognosis in OSCC have not been reported in detail. Materials and methods: We isolated OSCC cells and performed single-cell RNA sequencing (scRNA-seq). We used immunohistochemistry (IHC) to analyze the relationship between TLSs and prognosis. Multiplex immunohistochemistry (MIHC), flow cytometry (FCM) and spatial analysis were performed to verify the characteristics of TCF1/TCF7+ T cells. The prognostic significance and upstream regulatory network of the TCF1/TCF7+ T cell subpopulation were determined by multivariate analysis and Scenic software. Results: We found a strong association between TCF1/TCF7+ T cell subsets, TLSs and prognosis. The results suggested that TCF1/TCF7+ T cells express high levels of TLS-related genes and low levels of immune checkpoint molecules. Finally, we found that TCF1/TCF7+ T cells were significantly associated with favorable outcomes. We also describe the upstream drivers that these cells rely on. Conclusions: TCF1/TCF7+ T cells could be used as a new therapeutic target to regulate the immune response of OSCC and are expected to be a new prognostic marker.