人类组织淋巴细胞的转录图谱揭示了肿瘤浸润性调节性T细胞的独特性。
Transcriptional Landscape of Human Tissue Lymphocytes Unveils Uniqueness of Tumor-Infiltrating T Regulatory Cells.
作者信息
De Simone Marco, Arrigoni Alberto, Rossetti Grazisa, Gruarin Paola, Ranzani Valeria, Politano Claudia, Bonnal Raoul J P, Provasi Elena, Sarnicola Maria Lucia, Panzeri Ilaria, Moro Monica, Crosti Mariacristina, Mazzara Saveria, Vaira Valentina, Bosari Silvano, Palleschi Alessandro, Santambrogio Luigi, Bovo Giorgio, Zucchini Nicola, Totis Mauro, Gianotti Luca, Cesana Giancarlo, Perego Roberto A, Maroni Nirvana, Pisani Ceretti Andrea, Opocher Enrico, De Francesco Raffaele, Geginat Jens, Stunnenberg Hendrik G, Abrignani Sergio, Pagani Massimiliano
机构信息
Istituto Nazionale Genetica Molecolare INGM 'Romeo ed Enrica Invernizzi,' Milan 20122, Italy.
Istituto Nazionale Genetica Molecolare INGM 'Romeo ed Enrica Invernizzi,' Milan 20122, Italy; Division of Pathology, IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan 20122, Italy; Department of Pathophysiology and Organ Transplantation, Università degli Studi di Milano, Milano 20122, Italy.
出版信息
Immunity. 2016 Nov 15;45(5):1135-1147. doi: 10.1016/j.immuni.2016.10.021.
Tumor-infiltrating regulatory T lymphocytes (Treg) can suppress effector T cells specific for tumor antigens. Deeper molecular definitions of tumor-infiltrating-lymphocytes could thus offer therapeutic opportunities. Transcriptomes of T helper 1 (Th1), Th17, and Treg cells infiltrating colorectal or non-small-cell lung cancers were compared to transcriptomes of the same subsets from normal tissues and validated at the single-cell level. We found that tumor-infiltrating Treg cells were highly suppressive, upregulated several immune-checkpoints, and expressed on the cell surfaces specific signature molecules such as interleukin-1 receptor 2 (IL1R2), programmed death (PD)-1 Ligand1, PD-1 Ligand2, and CCR8 chemokine, which were not previously described on Treg cells. Remarkably, high expression in whole-tumor samples of Treg cell signature genes, such as LAYN, MAGEH1, or CCR8, correlated with poor prognosis. Our findings provide insights into the molecular identity and functions of human tumor-infiltrating Treg cells and define potential targets for tumor immunotherapy.
肿瘤浸润调节性T淋巴细胞（Treg）可抑制针对肿瘤抗原的效应T细胞。因此，对肿瘤浸润淋巴细胞进行更深入的分子定义可能带来治疗机会。将浸润结直肠癌或非小细胞肺癌的辅助性T细胞1（Th1）、Th17和Treg细胞的转录组与正常组织中相同亚群的转录组进行比较，并在单细胞水平进行验证。我们发现，肿瘤浸润Treg细胞具有高度抑制性，上调了多个免疫检查点，并在细胞表面表达特定的标志性分子，如白细胞介素-1受体2（IL1R2）、程序性死亡（PD）-1配体1、PD-1配体2和CCR8趋化因子，这些分子此前未在Treg细胞上被描述过。值得注意的是，Treg细胞标志性基因（如LAYN、MAGEH1或CCR8）在全肿瘤样本中的高表达与预后不良相关。我们的研究结果为人类肿瘤浸润Treg细胞的分子特征和功能提供了见解，并确定了肿瘤免疫治疗的潜在靶点。
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