High proportion of PD-1 and CD39 positive CD8+ tissue resident T lymphocytes correlates with better clinical outcome in resected human oesophageal adenocarcinoma
High proportion of PD-1 and CD39 positive CD8+ tissue resident T lymphocytes correlates with better clinical outcome in resected human oesophageal adenocarcinoma
Objective: to understand the CD8+ tumour infiltrating lymphocyte (TIL) compartment of oesophageal adenocarcinoma (OAC) with regards to markers of lymphocyte exhaustion, tissue residency and to identify possible reasons behind differential responses to therapy.
Design: tumour samples from 44 patients undergoing curative resection for OAC were assessed by flow cytometry for presence of antigen-experienced TILs and markers of activation and exhaustion. Populations of PD-1 and CD39 positive OAC TILs were sorted, and bulk RNA sequencing undertaken using a modified SmartSeq2 protocol. Flow cytometric assessment of functionality was completed.
Results: a higher proportion of antigen experienced CD8+ OAC TILs was associated with improved survival following surgery; while, high double positivity (DP) for PD-1 and CD39 among these TILs also correlated significantly with outcome. These DP TILs possess a minority population which is positive for the markers of exhaustion TIM3 and LAG3. Transcriptomic assessment of the PD-1 and CD39 DP TILs demonstrated enrichment for a tissue resident memory T lymphocyte (TRM) phenotype associated with improved survival in other cancers, reinforced by positivity for the canonical TRM marker CD103 by flow cytometry. This population demonstrated maintained functional capacity both in their transcriptomic profile, and on flow cytometric assessment, as well as preserved proliferative capacity.
Conclusion: resected OAC are variably infiltrated by PD-1 and CD39 DP TILs, an abundance of which among lymphocytes is associated with improved survival. This DP population has an increased, but still modest, frequency of TIM3 and LAG3 positivity compared to DN, and is in keeping with a functionally competent TRM phenotype.
Hill, Samuel L.
72d727e6-0e71-4e35-8dc3-7123650800b5
Sugiyarto, Gessa
571d4680-798b-45e1-9e8b-9990f6ec53bd
Harrington, Jack
1637c289-2191-454a-a600-464b829850b1
James, Edd
7dc1afb7-d326-4050-89fc-1f4e2a1a19a4
Underwood, Timothy J.
8e81bf60-edd2-4b0e-8324-3068c95ea1c6
Elliott, Tim
16670fa8-c2f9-477a-91df-7c9e5b453e0e
5 September 2024
Hill, Samuel L.
72d727e6-0e71-4e35-8dc3-7123650800b5
Sugiyarto, Gessa
571d4680-798b-45e1-9e8b-9990f6ec53bd
Harrington, Jack
1637c289-2191-454a-a600-464b829850b1
James, Edd
7dc1afb7-d326-4050-89fc-1f4e2a1a19a4
Underwood, Timothy J.
8e81bf60-edd2-4b0e-8324-3068c95ea1c6
Elliott, Tim
16670fa8-c2f9-477a-91df-7c9e5b453e0e
Hill, Samuel L., Sugiyarto, Gessa, Harrington, Jack, James, Edd, Underwood, Timothy J. and Elliott, Tim
(2024)
High proportion of PD-1 and CD39 positive CD8+ tissue resident T lymphocytes correlates with better clinical outcome in resected human oesophageal adenocarcinoma.
Cancer Immunology Immunotherapy, 73, [213].
(doi:10.1007/s00262-024-03799-y).
Abstract
Objective: to understand the CD8+ tumour infiltrating lymphocyte (TIL) compartment of oesophageal adenocarcinoma (OAC) with regards to markers of lymphocyte exhaustion, tissue residency and to identify possible reasons behind differential responses to therapy.
Design: tumour samples from 44 patients undergoing curative resection for OAC were assessed by flow cytometry for presence of antigen-experienced TILs and markers of activation and exhaustion. Populations of PD-1 and CD39 positive OAC TILs were sorted, and bulk RNA sequencing undertaken using a modified SmartSeq2 protocol. Flow cytometric assessment of functionality was completed.
Results: a higher proportion of antigen experienced CD8+ OAC TILs was associated with improved survival following surgery; while, high double positivity (DP) for PD-1 and CD39 among these TILs also correlated significantly with outcome. These DP TILs possess a minority population which is positive for the markers of exhaustion TIM3 and LAG3. Transcriptomic assessment of the PD-1 and CD39 DP TILs demonstrated enrichment for a tissue resident memory T lymphocyte (TRM) phenotype associated with improved survival in other cancers, reinforced by positivity for the canonical TRM marker CD103 by flow cytometry. This population demonstrated maintained functional capacity both in their transcriptomic profile, and on flow cytometric assessment, as well as preserved proliferative capacity.
Conclusion: resected OAC are variably infiltrated by PD-1 and CD39 DP TILs, an abundance of which among lymphocytes is associated with improved survival. This DP population has an increased, but still modest, frequency of TIM3 and LAG3 positivity compared to DN, and is in keeping with a functionally competent TRM phenotype.
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Hill - 2024 - Cancer Immunology Immunotherapy - High proportion of PD-1 and CD39 TIL
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Accepted/In Press date: 1 August 2024
Published date: 5 September 2024
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Local EPrints ID: 498429
URI: http://eprints.soton.ac.uk/id/eprint/498429
ISSN: 0340-7004
PURE UUID: ccd5791d-1414-4ae7-a63e-229ea853a3f2
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Date deposited: 18 Feb 2025 17:39
Last modified: 19 Feb 2025 02:41
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Author:
Samuel L. Hill
Author:
Gessa Sugiyarto
Author:
Jack Harrington
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