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泛癌单细胞转录组聚类揭示了具有不同免疫检查点抑制剂反应的异质性耗竭CD8 T细胞群体。

Pan-cancer single cell transcriptomic clustering reveals heterogeneous CD8 exhausted T cell populations with different immune checkpoint inhibitor responses.

作者信息

Mu Rui, Barakat Rasha, Gutmann David H

机构信息

Department of Neurology, Washington University, St. Louis, MO, USA.

出版信息

Oncoimmunology. 2025 Dec;14(1):2540504. doi: 10.1080/2162402X.2025.2540504. Epub 2025 Aug 3.


DOI:10.1080/2162402X.2025.2540504
PMID:40753639
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12320814/
Abstract

In most cancers, T lymphocytes comprise an essential cellular component of the non-neoplastic microenvironment, where they have the capacity to both suppress and support tumor growth. One specialized T lymphocyte population is the CD8 exhausted T cell, which has been intensely studied as an actionable therapeutic target. Unfortunately, there is currently no uniformly accepted classification scheme for these specialized T cells. To provide a potential model for classifying CD8 exhausted T cells, we leveraged single cell transcriptomic analysis of a diverse collection of both human ( = 8) and mouse ( = 4) cancers to identify unique subpopulations shared across tumor types and species. By integrating data from both human and mouse cancer studies, as well as previously described CD8 exhausted T cell subsets, we provide an integrated framework to characterize the heterogeneity of exhausted CD8 T cells. As such, one of these subpopulations (cluster C1) increases following immune checkpoint inhibitor treatment in the setting of cancer in mice and patients. Taken together, this proposed classification scheme may be useful for the design and interpretation of current and future immune-based therapy studies.

摘要

在大多数癌症中,T淋巴细胞是非肿瘤微环境的重要细胞组成部分,它们既有抑制肿瘤生长的能力,也有促进肿瘤生长的能力。一种特殊的T淋巴细胞群体是CD8耗竭性T细胞,它作为一个可操作的治疗靶点受到了深入研究。不幸的是,目前对于这些特殊的T细胞尚无统一认可的分类方案。为了提供一种潜在的CD8耗竭性T细胞分类模型,我们利用对多种人类(n = 8)和小鼠(n = 4)癌症样本进行的单细胞转录组分析,来识别跨肿瘤类型和物种共享的独特亚群。通过整合来自人类和小鼠癌症研究的数据,以及先前描述的CD8耗竭性T细胞亚群,我们提供了一个综合框架来描述耗竭性CD8 T细胞的异质性。因此,其中一个亚群(C1簇)在小鼠和患者癌症免疫检查点抑制剂治疗后会增加。综上所述,这种提议的分类方案可能有助于当前和未来基于免疫疗法研究的设计和解释。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8b7/12320814/252b09995d6a/KONI_A_2540504_F0006_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8b7/12320814/0ce54be35104/KONI_A_2540504_F0001_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8b7/12320814/b32f31806a6b/KONI_A_2540504_F0002_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8b7/12320814/c6313b212877/KONI_A_2540504_F0003_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8b7/12320814/1705ae92fb0f/KONI_A_2540504_F0004_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8b7/12320814/a06622fff89a/KONI_A_2540504_F0005_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8b7/12320814/252b09995d6a/KONI_A_2540504_F0006_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8b7/12320814/0ce54be35104/KONI_A_2540504_F0001_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8b7/12320814/b32f31806a6b/KONI_A_2540504_F0002_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8b7/12320814/c6313b212877/KONI_A_2540504_F0003_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8b7/12320814/1705ae92fb0f/KONI_A_2540504_F0004_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8b7/12320814/a06622fff89a/KONI_A_2540504_F0005_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8b7/12320814/252b09995d6a/KONI_A_2540504_F0006_OC.jpg

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本文引用的文献

[1]
Mapping the genetic landscape establishing a tumor immune microenvironment favorable for anti-PD-1 response.

Cell Rep. 2025-5-27

[2]
The diversity of CD8 T cell dysfunction in cancer and viral infection.

Nat Rev Immunol. 2025-4-11

[3]
Human single cell RNA-sequencing reveals a targetable CD8 exhausted T cell population that maintains mouse low-grade glioma growth.

Nat Commun. 2024-11-28

[4]
T cell dysfunction and therapeutic intervention in cancer.

Nat Immunol. 2024-8

[5]
Maternal obesogenic diet operates at the tumor cell of origin to increase incidence and decrease latency of neurofibromatosis type 1 optic pathway glioma.

Neuro Oncol. 2024-12-5

[6]
Osr2 functions as a biomechanical checkpoint to aggravate CD8 T cell exhaustion in tumor.

Cell. 2024-6-20

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NF1 mutation-driven neuronal hyperexcitability sets a threshold for tumorigenesis and therapeutic targeting of murine optic glioma.

Neuro Oncol. 2024-8-5

[8]
CD8 T cells in the cancer-immunity cycle.

Immunity. 2023-10-10

[9]
Sex-Biased T-cell Exhaustion Drives Differential Immune Responses in Glioblastoma.

Cancer Discov. 2023-9-6

[10]
Pan-cancer T cell atlas links a cellular stress response state to immunotherapy resistance.

Nat Med. 2023-6

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