Immune-awakening revealed by peripheral T cell dynamics after one cycle of immunotherapy.

Humans Immunologic Factors / therapeutic use Immunotherapy Leukocytes, Mononuclear Melanoma / therapy Receptors, Antigen, T-Cell / genetics

Journal

Nature cancer
ISSN: 2662-1347
Titre abrégé: Nat Cancer
Pays: England
ID NLM: 101761119

Informations de publication

Date de publication:
02 2020
Historique:
entrez: 29 2 2020
pubmed: 29 2 2020
medline: 29 2 2020
Statut: ppublish

Résumé

Our understanding of how checkpoint inhibitors (CPI) affect T cell evolution is incomplete, limiting our ability to achieve full clinical benefit from these drugs. Here we analyzed peripheral T cell populations after one cycle of CPI and identified a dynamic awakening of the immune system revealed by T cell evolution in response to treatment. We sequenced T cell receptors (TCR) in plasma cell-free DNA (cfDNA) and peripheral blood mononuclear cells (PBMC) and performed phenotypic analysis of peripheral T cell subsets from metastatic melanoma patients treated with CPI. We found that early peripheral T cell turnover and TCR repertoire dynamics identified which patients would respond to treatment. Additionally, the expansion of a subset of immune-effector peripheral T cells we call T

Identifiants

DOI: 10.1038/s43018-019-0022-x PMID: 32110781 PMC: PMC7046489
pubmed: 32110781
doi: 10.1038/s43018-019-0022-x
pmc: PMC7046489
mid: EMS85253
pii: 10.1038/s43018-019-0022-x
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

Pagination

210-221

Subventions

Organisme : Wellcome Trust
ID : 100282
Pays : United Kingdom
Organisme : Cancer Research UK
ID : A22902
Pays : United Kingdom
Organisme : Cancer Research UK
ID : A27412
Pays : United Kingdom

Commentaires et corrections

Type : CommentIn

Déclaration de conflit d'intérêts

Conflict of Interest: RM is a consultant for Pfizer and has a drug discovery programme with Basilea Pharmaceutica. PL serves as 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.

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Auteurs

Sara Valpione (S)

Molecular Oncology Group, Cancer Research UK Manchester Institute, The University of Manchester, Alderley Park, UK.
The Christie NHS Foundation Trust, Manchester, UK.

Elena Galvani (E)

Molecular Oncology Group, Cancer Research UK Manchester Institute, The University of Manchester, Alderley Park, UK.

Joshua Tweedy (J)

Molecular Oncology Group, Cancer Research UK Manchester Institute, The University of Manchester, Alderley Park, UK.

Piyushkumar A Mundra (PA)

Molecular Oncology Group, Cancer Research UK Manchester Institute, The University of Manchester, Alderley Park, UK.
ORCID: 0000-0001-7769-2939

Antonia Banyard (A)

Advanced Imaging and Flow Cytometry, Cancer Research UK Manchester Institute, The University of Manchester, Alderley Park, UK.

Philippa Middlehurst (P)

Manchester Cancer Research Centre Biobank, The Christie NHS Foundation Trust, Manchester, UK.

Jeff Barry (J)

Advanced Imaging and Flow Cytometry, Cancer Research UK Manchester Institute, The University of Manchester, Alderley Park, UK.

Sarah Mills (S)

Manchester Cancer Research Centre Biobank, The Christie NHS Foundation Trust, Manchester, UK.

Zena Salih (Z)

The Christie NHS Foundation Trust, Manchester, UK.

John Weightman (J)

Molecular Biology Core Facility, Cancer Research UK Manchester Institute, The University of Manchester, Alderley Park, UK.

Avinash Gupta (A)

The Christie NHS Foundation Trust, Manchester, UK.

Gabriela Gremel (G)

Molecular Oncology Group, Cancer Research UK Manchester Institute, The University of Manchester, Alderley Park, UK.
Boehringer Ingelheim, Vienna, Austria.

Franziska Baenke (F)

Molecular Oncology Group, Cancer Research UK Manchester Institute, The University of Manchester, Alderley Park, UK.
German Cancer Consortium (DKTK), German Cancer Research Centre (DKFZ), Heidelberg, Germany.
Department of Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus, Technical University Dresden, Dresden, Germany.

Nathalie Dhomen (N)

Molecular Oncology Group, Cancer Research UK Manchester Institute, The University of Manchester, Alderley Park, UK.

Paul C Lorigan (PC)

The Christie NHS Foundation Trust, Manchester, UK. paul.lorigan@christie.nhs.uk.
ORCID: 0000-0002-8875-2164

Richard Marais (R)

Molecular Oncology Group, Cancer Research UK Manchester Institute, The University of Manchester, Alderley Park, UK. richard.marais@cruk.manchester.ac.uk.
ORCID: 0000-0001-7484-4183

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Immune-awakening revealed by peripheral T cell...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Effets physiologiques des médicaments › Facteurs immunologiques › Immune-awakening revealed by peripheral T cell...
questionsmedicales.fr › Thérapeutique › Biothérapie › Immunothérapie › Immune-awakening revealed by peripheral T cell...
questionsmedicales.fr › Systèmes sanguin et immunitaire › Système immunitaire › Leucocytes › Agranulocytes › Immune-awakening revealed by peripheral T cell...
questionsmedicales.fr › Tumeurs › Tumeurs par type histologique › Naevus et mélanomes › Mélanome › Immune-awakening revealed by peripheral T cell...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Récepteurs de surface cellulaire › Récepteurs immunologiques › Récepteurs aux antigènes › Récepteurs aux antigènes des cellules T › Immune-awakening revealed by peripheral T cell...