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癌症免疫疗法在治疗非小细胞肺癌方面表现出持续的临床反应，但效果各不相同，部分取决于肿瘤浸润淋巴细胞的数量和性质。为了描绘肿瘤浸润淋巴细胞的组成，谱系和功能状态的基线情况，我们在这里对来自14名未接受过治疗的非小细胞肺癌患者的12,346个T细胞进行了深度单细胞RNA测序。联合表达和基于T细胞抗原受体的谱系追踪揭示了显着比例的具有高度迁移性质的组织间效应T细胞。除了经历用尽的肿瘤浸润性CD8 T细胞外，我们观察到两组细胞在耗尽前表现出状态，并且“预先耗尽”与耗尽的T细胞的高比率与肺腺癌的更好预后相关。另外，我们观察到肿瘤调节性T细胞（Tregs）内的进一步异质性，其特征在于TNFRSF9的双峰分布，TNFRSF9是抗原特异性Treg的活化标记。这些活化的肿瘤Tregs（包括IL1R2）的基因特征与肺腺癌预后不良相关。我们的研究为患者分层提供了一种新方法，有助于进一步了解肺癌中T细胞的功能状态和动态。 Cancer immunotherapies have shown sustained clinical responses in treating non-small-cell lung cancer1–3, but effi- cacy varies and depends in part on the amount and properties of tumor infiltrating lymphocytes4–6. To depict the baseline landscape of the composition, lineage and functional states of tumor infiltrating lymphocytes, here we performed deep single-cell RNA sequencing for 12,346 T cells from 14 treat- ment-naïve non-small-cell lung cancer patients. Combined expression and T cell antigen receptor based lineage track- ing revealed a significant proportion of inter-tissue effector T cells with a highly migratory nature. As well as tumor-infil- trating CD8 T cells undergoing exhaustion, we observed two clusters of cells exhibiting states preceding exhaustion, and a high ratio of “pre-exhausted” to exhausted T cells was associated with better prognosis of lung adenocarcinoma. Additionally, we observed further heterogeneity within the tumor regulatory T cells (Tregs), characterized by the bimodal distribution of TNFRSF9, an activation marker for antigen- specific Tregs. The gene signature of those activated tumor Tregs, which included IL1R2, correlated with poor prognosis in lung adenocarcinoma. Our study provides a new approach for patient stratification and will help further understand the functional states and dynamics of T cells in lung cancer. 本微信所有转载文章系出于传递更多信息之目的，且明确注明来源和作者，不希望被转载的媒体或个人可与我们联系，我们将立即进行删除处理。 |
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