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Tissue-resident memory features are linked to the magnitude of cytotoxic T cell responses in human lung cancer

Tissue-resident memory features are linked to the magnitude of cytotoxic T cell responses in human lung cancer
Tissue-resident memory features are linked to the magnitude of cytotoxic T cell responses in human lung cancer

Therapies that boost the anti-tumor responses of cytotoxic T lymphocytes (CTLs) have shown promise; however, clinical responses to the immunotherapeutic agents currently available vary considerably, and the molecular basis of this is unclear. We performed transcriptomic profiling of tumor-infiltrating CTLs from treatment-naive patients with lung cancer to define the molecular features associated with the robustness of anti-tumor immune responses. We observed considerable heterogeneity in the expression of molecules associated with activation of the T cell antigen receptor (TCR) and of immunological-checkpoint molecules such as 4-1BB, PD-1 and TIM-3. Tumors with a high density of CTLs showed enrichment for transcripts linked to tissue-resident memory cells (TRM cells), such as CD103, and CTLs from CD103(hi) tumors displayed features of enhanced cytotoxicity. A greater density of TRM cells in tumors was predictive of a better survival outcome in lung cancer, and this effect was independent of that conferred by CTL density. Here we define the 'molecular fingerprint' of tumor-infiltrating CTLs and identify potentially new targets for immunotherapy.

Journal Article
1529-2908
Ganesan, Anusha-Preethi
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Clarke, James
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Wood, Oliver
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Garrido-Martin, Eva M
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Chee, Serena J.
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Mellows, Toby
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Samaniego-Castruita, Daniela
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Singh, Divya
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Seumois, Grégory
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Alzetani, Aiman
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Woo, Edwin
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Friedmann, Peter S
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King, Emma V
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Thomas, Gareth J
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Sanchez-Elsner, Tilman
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Vijayanand, Pandurangan
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Ottensmeier, Christian H
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Ganesan, Anusha-Preethi
bd39158f-6730-42fa-ba38-1d27885acb52
Clarke, James
f1c46d41-f18e-4e72-9b4f-437d520db1f7
Wood, Oliver
dad2f90c-70a5-44a0-914a-52809b75d1c6
Garrido-Martin, Eva M
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Chee, Serena J.
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Mellows, Toby
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Samaniego-Castruita, Daniela
e0925b0f-9b07-46e3-a433-08a941e11c6f
Singh, Divya
ec02f7f5-fa4a-4dde-a838-eb9adf8e9210
Seumois, Grégory
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Alzetani, Aiman
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Woo, Edwin
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Friedmann, Peter S
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King, Emma V
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Thomas, Gareth J
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Sanchez-Elsner, Tilman
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Vijayanand, Pandurangan
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Ottensmeier, Christian H
42b8a398-baac-4843-a3d6-056225675797

Ganesan, Anusha-Preethi, Clarke, James, Wood, Oliver, Garrido-Martin, Eva M, Chee, Serena J., Mellows, Toby, Samaniego-Castruita, Daniela, Singh, Divya, Seumois, Grégory, Alzetani, Aiman, Woo, Edwin, Friedmann, Peter S, King, Emma V, Thomas, Gareth J, Sanchez-Elsner, Tilman, Vijayanand, Pandurangan and Ottensmeier, Christian H (2017) Tissue-resident memory features are linked to the magnitude of cytotoxic T cell responses in human lung cancer. Nature Immunology. (doi:10.1038/ni.3775).

Record type: Article

Abstract

Therapies that boost the anti-tumor responses of cytotoxic T lymphocytes (CTLs) have shown promise; however, clinical responses to the immunotherapeutic agents currently available vary considerably, and the molecular basis of this is unclear. We performed transcriptomic profiling of tumor-infiltrating CTLs from treatment-naive patients with lung cancer to define the molecular features associated with the robustness of anti-tumor immune responses. We observed considerable heterogeneity in the expression of molecules associated with activation of the T cell antigen receptor (TCR) and of immunological-checkpoint molecules such as 4-1BB, PD-1 and TIM-3. Tumors with a high density of CTLs showed enrichment for transcripts linked to tissue-resident memory cells (TRM cells), such as CD103, and CTLs from CD103(hi) tumors displayed features of enhanced cytotoxicity. A greater density of TRM cells in tumors was predictive of a better survival outcome in lung cancer, and this effect was independent of that conferred by CTL density. Here we define the 'molecular fingerprint' of tumor-infiltrating CTLs and identify potentially new targets for immunotherapy.

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Accepted/In Press date: 22 May 2017
e-pub ahead of print date: 19 June 2017
Keywords: Journal Article

Identifiers

Local EPrints ID: 413321
URI: https://eprints.soton.ac.uk/id/eprint/413321
ISSN: 1529-2908
PURE UUID: fb3c9857-457d-4ec6-b1de-93ef6285bab8

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Date deposited: 21 Aug 2017 16:31
Last modified: 10 Dec 2019 05:56

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Contributors

Author: Anusha-Preethi Ganesan
Author: James Clarke
Author: Oliver Wood
Author: Eva M Garrido-Martin
Author: Serena J. Chee
Author: Toby Mellows
Author: Daniela Samaniego-Castruita
Author: Divya Singh
Author: Grégory Seumois
Author: Aiman Alzetani
Author: Edwin Woo
Author: Peter S Friedmann
Author: Emma V King
Author: Gareth J Thomas
Author: Pandurangan Vijayanand

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