Clarke, James, Panwar, Bharat, Madrigal, Ariel, Singh, Divya, Gujar, Ravindra, Wood, Oliver, Chee, Serena J, Eschweiler, Simon, King, Emma V, Awad, Amiera S et al (show 13 more authors)
(2019)
Single-cell transcriptomic analysis of tissue-resident memory T cells in human lung cancer.
JOURNAL OF EXPERIMENTAL MEDICINE, 216 (9).
pp. 2128-2149.
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Abstract
High numbers of tissue-resident memory T (TRM) cells are associated with better clinical outcomes in cancer patients. However, the molecular characteristics that drive their efficient immune response to tumors are poorly understood. Here, single-cell and bulk transcriptomic analysis of TRM and non-TRM cells present in tumor and normal lung tissue from patients with lung cancer revealed that PD-1–expressing TRM cells in tumors were clonally expanded and enriched for transcripts linked to cell proliferation and cytotoxicity when compared with PD-1–expressing non-TRM cells. This feature was more prominent in the TRM cell subset coexpressing PD-1 and TIM-3, and it was validated by functional assays ex vivo and also reflected in their chromatin accessibility profile. This PD-1+TIM-3+ TRM cell subset was enriched in responders to PD-1 inhibitors and in tumors with a greater magnitude of CTL responses. These data highlight that not all CTLs expressing PD-1 are dysfunctional; on the contrary, TRM cells with PD-1 expression were enriched for features suggestive of superior functionality.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | Lung, Lymphocyte Subsets, T-Lymphocytes, Lymphocytes, Tumor-Infiltrating, Clone Cells, Humans, Lung Neoplasms, RNA, Messenger, Gene Expression Profiling, Cell Proliferation, Cytotoxicity, Immunologic, Immunologic Memory, Transcription, Genetic, Single-Cell Analysis, Programmed Cell Death 1 Receptor, Transcriptome, Hepatitis A Virus Cellular Receptor 2 |
| Divisions: | Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 18 Apr 2023 15:36 |
| Last Modified: | 18 Apr 2023 15:36 |
| DOI: | 10.1084/jem.20190249 |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3169668 |
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