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单细胞分析鉴定出循环抗肿瘤 CD8 T 细胞及其富集标志物。

Single-cell analyses identify circulating anti-tumor CD8 T cells and markers for their enrichment.

机构信息

Department of Immunology, Blavatnik Institute, Harvard Medical School, Boston, MA.

Evergrande Center for Immunological Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA.

出版信息

J Exp Med. 2021 Apr 5;218(4). doi: 10.1084/jem.20200920.

DOI:10.1084/jem.20200920
PMID:33651880
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7933992/
Abstract

The ability to monitor anti-tumor CD8+ T cell responses in the blood has tremendous therapeutic potential. Here, we used paired single-cell RNA and TCR sequencing to detect and characterize "tumor-matching" (TM) CD8+ T cells in the blood of mice with MC38 tumors or melanoma patients using the TCR as a molecular barcode. TM cells showed increased activation compared with nonmatching T cells in blood and were less exhausted than matching cells in tumors. Importantly, PD-1, which has been used to identify putative circulating anti-tumor CD8+ T cells, showed poor sensitivity for identifying TM cells. By leveraging the transcriptome, we identified candidate cell surface markers for TM cells in mice and patients and validated NKG2D, CD39, and CX3CR1 in mice. These data show that the TCR can be used to identify tumor-relevant cells for characterization, reveal unique transcriptional properties of TM cells, and develop marker panels for tracking and analysis of these cells.

摘要

监测血液中抗肿瘤 CD8+ T 细胞反应的能力具有巨大的治疗潜力。在这里，我们使用配对的单细胞 RNA 和 TCR 测序，使用 TCR 作为分子条码，在患有 MC38 肿瘤的小鼠或黑色素瘤患者的血液中检测和表征“肿瘤匹配”（TM）CD8+ T 细胞。与血液中的非匹配 T 细胞相比，TM 细胞表现出更高的激活水平，并且比肿瘤中的匹配细胞的衰竭程度更低。重要的是，已用于识别潜在循环抗肿瘤 CD8+ T 细胞的 PD-1，在识别 TM 细胞方面的灵敏度较差。通过利用转录组，我们在小鼠和患者中鉴定出 TM 细胞的候选细胞表面标志物，并在小鼠中验证了 NKG2D、CD39 和 CX3CR1。这些数据表明，TCR 可用于鉴定用于表征的肿瘤相关细胞，揭示 TM 细胞的独特转录特性，并开发用于跟踪和分析这些细胞的标记物面板。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb0b/7933992/01c4f2fbd032/JEM_20200920_FigS5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb0b/7933992/1914c8476cbb/JEM_20200920_GA.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb0b/7933992/602f130167f8/JEM_20200920_Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb0b/7933992/4fda1c64f838/JEM_20200920_FigS1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb0b/7933992/1a4f68d46114/JEM_20200920_Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb0b/7933992/31d9c92522a0/JEM_20200920_FigS2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb0b/7933992/10432d06bede/JEM_20200920_FigS3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb0b/7933992/2ed13fa253b9/JEM_20200920_Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb0b/7933992/c444c39d8e6d/JEM_20200920_FigS4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb0b/7933992/c7dec931dcad/JEM_20200920_Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb0b/7933992/ee8fb7ed0365/JEM_20200920_Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb0b/7933992/1c7e2e79a805/JEM_20200920_Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb0b/7933992/01c4f2fbd032/JEM_20200920_FigS5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb0b/7933992/1914c8476cbb/JEM_20200920_GA.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb0b/7933992/602f130167f8/JEM_20200920_Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb0b/7933992/4fda1c64f838/JEM_20200920_FigS1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb0b/7933992/1a4f68d46114/JEM_20200920_Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb0b/7933992/31d9c92522a0/JEM_20200920_FigS2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb0b/7933992/10432d06bede/JEM_20200920_FigS3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb0b/7933992/2ed13fa253b9/JEM_20200920_Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb0b/7933992/c444c39d8e6d/JEM_20200920_FigS4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb0b/7933992/c7dec931dcad/JEM_20200920_Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb0b/7933992/ee8fb7ed0365/JEM_20200920_Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb0b/7933992/1c7e2e79a805/JEM_20200920_Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb0b/7933992/01c4f2fbd032/JEM_20200920_FigS5.jpg

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本文引用的文献

[1]
Circulating clonally expanded T cells reflect functions of tumor-infiltrating T cells.

J Exp Med. 2021-4-5

[2]
Bayesian model selection reveals biological origins of zero inflation in single-cell transcriptomics.

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Immunity. 2020-5-11

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