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Single-cell transcriptomic analysis of tissue-resident memory T cells in human lung cancer

Single-cell transcriptomic analysis of tissue-resident memory T cells in human lung cancer
Single-cell transcriptomic analysis of tissue-resident memory T cells in human lung cancer
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.
0022-1007
2128-2149
Clarke, James
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Panwar, Bharat
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Madrigal, Ariel
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Singh, Divya
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Gujar, Ravindra
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Wood, Oliver
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Chee, Serena, Jamie Tzu Wen
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Eschweiler, Simon
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King, Emma
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Awad, Amiera
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Hanley, Christopher
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Mccann, Katy
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Bhattacharyya, Sourya
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Woo, Edwin
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Alzetani, Aiman
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Seumois, Gregory
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Thomas, Gareth
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Ganesan, Anusha-Preethi
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Friedmann, Peter
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Sanchez-Elsner, Tilman
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Ay, Ferhat
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Ottensmeier, Christian
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Vijayanand, Pandurangan
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Clarke, James
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Panwar, Bharat
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Madrigal, Ariel
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Singh, Divya
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Gujar, Ravindra
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Wood, Oliver
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Chee, Serena, Jamie Tzu Wen
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Eschweiler, Simon
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King, Emma
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Awad, Amiera
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Hanley, Christopher
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Mccann, Katy
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Bhattacharyya, Sourya
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Woo, Edwin
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Alzetani, Aiman
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Seumois, Gregory
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Thomas, Gareth
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Ganesan, Anusha-Preethi
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Friedmann, Peter
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Sanchez-Elsner, Tilman
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Ay, Ferhat
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Ottensmeier, Christian
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Vijayanand, Pandurangan
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Clarke, James, Panwar, Bharat, Madrigal, Ariel, Singh, Divya, Gujar, Ravindra, Wood, Oliver, Chee, Serena, Jamie Tzu Wen, Eschweiler, Simon, King, Emma, Awad, Amiera, Hanley, Christopher, Mccann, Katy, Bhattacharyya, Sourya, Woo, Edwin, Alzetani, Aiman, Seumois, Gregory, Thomas, Gareth, Ganesan, Anusha-Preethi, Friedmann, Peter, Sanchez-Elsner, Tilman, Ay, Ferhat, Ottensmeier, Christian and Vijayanand, Pandurangan (2019) Single-cell transcriptomic analysis of tissue-resident memory T cells in human lung cancer. The Journal of Experimental Medicine, 216 (9), 2128-2149. (doi:10.1084/jem.20190249).

Record type: Article

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.

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Accepted/In Press date: 23 May 2019
e-pub ahead of print date: 21 June 2019
Published date: September 2019

Identifiers

Local EPrints ID: 431395
URI: http://eprints.soton.ac.uk/id/eprint/431395
ISSN: 0022-1007
PURE UUID: d3090513-ac40-445f-b51d-4436f36dc546
ORCID for Christopher Hanley: ORCID iD orcid.org/0000-0003-3816-7220
ORCID for Tilman Sanchez-Elsner: ORCID iD orcid.org/0000-0003-1915-2410

Catalogue record

Date deposited: 31 May 2019 16:30
Last modified: 26 Nov 2021 06:29

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Contributors

Author: James Clarke
Author: Bharat Panwar
Author: Ariel Madrigal
Author: Divya Singh
Author: Ravindra Gujar
Author: Oliver Wood
Author: Serena, Jamie Tzu Wen Chee
Author: Simon Eschweiler
Author: Emma King
Author: Amiera Awad
Author: Katy Mccann
Author: Sourya Bhattacharyya
Author: Edwin Woo
Author: Aiman Alzetani
Author: Gregory Seumois
Author: Gareth Thomas
Author: Anusha-Preethi Ganesan
Author: Peter Friedmann
Author: Ferhat Ay
Author: Pandurangan Vijayanand

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