Identification of a CD8+ T-cell response to a predicted neoantigen in malignant mesothelioma.


Journal

Oncoimmunology
ISSN: 2162-4011
Titre abrégé: Oncoimmunology
Pays: United States
ID NLM: 101570526

Informations de publication

Date de publication:
2020
Historique:
received: 12 08 2019
revised: 20 10 2019
accepted: 22 10 2019
entrez: 1 2 2020
pubmed: 1 2 2020
medline: 1 2 2020
Statut: epublish

Résumé

Neoantigens present unique and specific targets for personalized cancer immunotherapy strategies. Given the low mutational burden yet immunotherapy responsiveness of malignant mesothelioma (MM) when compared to other carcinogen-induced malignancies, identifying candidate neoantigens and T cells that recognize them has been a challenge. We used pleural effusions to gain access to MM tumor cells as well as immune cells in order to characterize the tumor-immune interface in MM. We characterized the landscape of potential neoantigens from SNVs identified in 27 MM patients and performed whole transcriptome sequencing of cell populations from 18 patient-matched pleural effusions. IFNγ ELISpot was performed to detect a CD8+ T cell responses to predicted neoantigens in one patient. We detected a median of 68 (range 7-258) predicted neoantigens across the samples. Wild-type non-binding to mutant binding predicted neoantigens increased risk of death in a model adjusting for age, sex, smoking status, histology and treatment (HR: 33.22, CI: 2.55-433.02,

Identifiants

pubmed: 32002298
doi: 10.1080/2162402X.2019.1684713
pii: 1684713
pmc: PMC6959430
doi:

Substances chimiques

Antigens, Neoplasm 0
ROBO3 protein, human 0
Receptors, Cell Surface 0

Types de publication

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

Langues

eng

Pagination

1684713

Informations de copyright

© 2019 The Author(s). Published with license by Taylor & Francis Group, LLC.

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Auteurs

Sophie Sneddon (S)

National Centre for Asbestos Related Disease, School of Medicine and Pharmacology, University of Western Australia, Nedlands, Australia.

Craig M Rive (CM)

National Centre for Asbestos Related Disease, School of Medicine and Pharmacology, University of Western Australia, Nedlands, Australia.

Shaokang Ma (S)

National Centre for Asbestos Related Disease, School of Medicine and Pharmacology, University of Western Australia, Nedlands, Australia.

Ian M Dick (IM)

National Centre for Asbestos Related Disease, School of Medicine and Pharmacology, University of Western Australia, Nedlands, Australia.

Richard J N Allcock (RJN)

Pathwest Laboratory Medicine, Western Australia, QEII Medical Centre, Nedlands, Australia.
School of Biomedical Sciences, University of Western Australia, Nedlands, Australia.

Scott D Brown (SD)

Michael Smith Genome Sciences Centre, BC Cancer, Vancouver, British Columbia, Canada.

Robert A Holt (RA)

Michael Smith Genome Sciences Centre, BC Cancer, Vancouver, British Columbia, Canada.

Mark Watson (M)

Institute for Immunology and Infectious Diseases, Murdoch University, Murdoch, Australia.

Shay Leary (S)

Institute for Immunology and Infectious Diseases, Murdoch University, Murdoch, Australia.

Y C Gary Lee (YCG)

National Centre for Asbestos Related Disease, School of Medicine and Pharmacology, University of Western Australia, Nedlands, Australia.
Department of Respiratory Medicine, Sir Charles Gairdner Hospital, Nedlands, Australia.

Bruce W S Robinson (BWS)

National Centre for Asbestos Related Disease, School of Medicine and Pharmacology, University of Western Australia, Nedlands, Australia.
Department of Respiratory Medicine, Sir Charles Gairdner Hospital, Nedlands, Australia.

Jenette Creaney (J)

National Centre for Asbestos Related Disease, School of Medicine and Pharmacology, University of Western Australia, Nedlands, Australia.

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