T cell immune awakening in response to immunotherapy is age-dependent.


Journal

European journal of cancer (Oxford, England : 1990)
ISSN: 1879-0852
Titre abrégé: Eur J Cancer
Pays: England
ID NLM: 9005373

Informations de publication

Date de publication:
02 2022
Historique:
received: 10 08 2021
revised: 29 10 2021
accepted: 08 11 2021
pubmed: 25 12 2021
medline: 22 4 2022
entrez: 24 12 2021
Statut: ppublish

Résumé

Precision immuno-oncology approaches are needed to improve cancer care. We recently demonstrated that in patients with metastatic melanoma, an increase of clonality or diversity of the T cell receptor (TCR) repertoire of peripheral T cells following one cycle of immunotherapy is coincident with response to immune-checkpoint blockade (ICB). We also identified a subset of peripheral CD8 Fifty patients with metastatic melanoma treated with first-line anti-PD-1 ICB were included. We analysed TCR repertoire and peripheral T We observed a correlation between T We demonstrate that immunotherapy-induced immune-awakening patterns in patients with melanoma are age-related and may impact patient response to ICB, and thus have implications for biomarker development and planning of personalised therapeutic strategies.

Sections du résumé

BACKGROUND
Precision immuno-oncology approaches are needed to improve cancer care. We recently demonstrated that in patients with metastatic melanoma, an increase of clonality or diversity of the T cell receptor (TCR) repertoire of peripheral T cells following one cycle of immunotherapy is coincident with response to immune-checkpoint blockade (ICB). We also identified a subset of peripheral CD8
METHODS
Fifty patients with metastatic melanoma treated with first-line anti-PD-1 ICB were included. We analysed TCR repertoire and peripheral T
RESULTS
We observed a correlation between T
CONCLUSIONS
We demonstrate that immunotherapy-induced immune-awakening patterns in patients with melanoma are age-related and may impact patient response to ICB, and thus have implications for biomarker development and planning of personalised therapeutic strategies.

Identifiants

pubmed: 34952479
pii: S0959-8049(21)01225-9
doi: 10.1016/j.ejca.2021.11.015
pmc: PMC8829752
pii:
doi:

Substances chimiques

Immunologic Factors 0
Receptors, Antigen, T-Cell 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

11-21

Subventions

Organisme : Cancer Research UK
ID : A22902
Pays : United Kingdom
Organisme : Cancer Research UK
ID : A27412
Pays : United Kingdom
Organisme : Department of Health
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 100282/Z/12/Z
Pays : United Kingdom

Informations de copyright

Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.

Déclaration de conflit d'intérêts

Conflict of interest statement RM is an expert witness for Pfizer. RM may benefit from drug discovery programmes that are commercialized. PL serves as a paid advisor/speaker for Bristol-Myers Squibb, Merck Sharp and Dohme, Roche, Novartis, Amgen, Pierre Fabre, Nektar, Melagenix. PL reports travel support from Bristol-Myers Squibb and Merck Sharp and Dohme, and receives research support from Bristol-Myers Squibb. AG received honoraria and consultancy fees from BMS and Novartis. All remaining authors have declared no conflicts of interest.

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Auteurs

Zena Salih (Z)

Molecular Oncology Group, Cancer Research UK Manchester Institute, The University of Manchester, Alderley Park, Macclesfield, Cheshire SK10 4TG, United Kingdom; The Christie NHS Foundation Trust, 550 Wilmslow Road, Manchester M20 4BX, United Kingdom.

Antonia Banyard (A)

Flow Cytometry, Cancer Research UK Manchester Institute, the University of Manchester, Alderley Park, Macclesfield, Cheshire SK10 4TG, United Kingdom.

Joshua Tweedy (J)

Molecular Oncology Group, Cancer Research UK Manchester Institute, The University of Manchester, Alderley Park, Macclesfield, Cheshire SK10 4TG, United Kingdom.

Elena Galvani (E)

Molecular Oncology Group, Cancer Research UK Manchester Institute, The University of Manchester, Alderley Park, Macclesfield, Cheshire SK10 4TG, United Kingdom.

Philippa Middlehurst (P)

Manchester Cancer Research Centre Biobank, The Christie NHS Foundation Trust, 550 Wilmslow Road, Manchester M20 4BX, United Kingdom.

Sarah Mills (S)

Manchester Cancer Research Centre Biobank, The Christie NHS Foundation Trust, 550 Wilmslow Road, Manchester M20 4BX, United Kingdom.

John Weightman (J)

Molecular Biology Core Facility, Cancer Research UK Manchester Institute, the University of Manchester, Alderley Park, Macclesfield, Cheshire SK10 4TG, United Kingdom.

Avinash Gupta (A)

The Christie NHS Foundation Trust, 550 Wilmslow Road, Manchester M20 4BX, United Kingdom.

Paul C Lorigan (PC)

The Christie NHS Foundation Trust, 550 Wilmslow Road, Manchester M20 4BX, United Kingdom; Division of Cancer Sciences, The University of Manchester, Oxford Road, Manchester M13 9PL, United Kingdom.

Cong Zhou (C)

Cancer Biomarker Centre, Cancer Research UK Manchester Institute, The University of Manchester, Alderley Park, Macclesfield, Cheshire SK10 4TG, United Kingdom.

Nathalie Dhomen (N)

Molecular Oncology Group, Cancer Research UK Manchester Institute, The University of Manchester, Alderley Park, Macclesfield, Cheshire SK10 4TG, United Kingdom.

Sara Valpione (S)

Molecular Oncology Group, Cancer Research UK Manchester Institute, The University of Manchester, Alderley Park, Macclesfield, Cheshire SK10 4TG, United Kingdom; The Christie NHS Foundation Trust, 550 Wilmslow Road, Manchester M20 4BX, United Kingdom.

Richard Marais (R)

Molecular Oncology Group, Cancer Research UK Manchester Institute, The University of Manchester, Alderley Park, Macclesfield, Cheshire SK10 4TG, United Kingdom. Electronic address: richard.marais@cruk.manchester.ac.uk.

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