Application of the pMHC array to characterise tumour antigen specific T cell populations in leukaemia patients at disease diagnosis

2.50
Hdl Handle:
http://hdl.handle.net/10547/600878
Title:
Application of the pMHC array to characterise tumour antigen specific T cell populations in leukaemia patients at disease diagnosis
Authors:
Brooks, Suzanne E.; Bonney, Stephanie A.; Lee, Cindy; Publicover, Amy; Khan, Ghazala; Smits, Evelien L.; Sigurdardottir, Dagmar; Arno, Matthew; Li, Demin; Mills, Ken I.; Pulford, Karen; Banham, Alison H.; van Tendeloo, Viggo; Mufti, Ghulam J.; Rammensee, Hans-Georg; Elliott, Tim J.; Orchard, Kim H.; Guinn, Barbara-Ann
Abstract:
Immunotherapy treatments for cancer are becoming increasingly successful, however to further improve our understanding of the T-cell recognition involved in effective responses and to encourage moves towards the development of personalised treatments for leukaemia immunotherapy, precise antigenic targets in individual patients have been identified. Cellular arrays using peptide-MHC (pMHC) tetramers allow the simultaneous detection of different antigen specific T-cell populations naturally circulating in patients and normal donors. We have developed the pMHC array to detect CD8+ T-cell populations in leukaemia patients that recognise epitopes within viral antigens (cytomegalovirus (CMV) and influenza (Flu)) and leukaemia antigens (including Per Arnt Sim domain 1 (PASD1), MelanA, Wilms’ Tumour (WT1) and tyrosinase). We show that the pMHC array is at least as sensitive as flow cytometry and has the potential to rapidly identify more than 40 specific T-cell populations in a small sample of T-cells (0.8–1.4 x 106). Fourteen of the twenty-six acute myeloid leukaemia (AML) patients analysed had T cells that recognised tumour antigen epitopes, and eight of these recognised PASD1 epitopes. Other tumour epitopes recognised were MelanA (n = 3), tyrosinase (n = 3) and WT1126-134 (n = 1). One of the seven acute lymphocytic leukaemia (ALL) patients analysed had T cells that recognised the MUC1950-958 epitope. In the future the pMHC array may be used provide point of care T-cell analyses, predict patient response to conventional therapy and direct personalised immunotherapy for patients.
Citation:
Brooks SE, Bonney SA, Lee C, Publicover A, Khan G, Smits EL, et al. (2015) Application of the pMHC Array to Characterise Tumour Antigen Specific T Cell Populations in Leukaemia Patients at Disease Diagnosis 2015, 10 (10):e0140483 PLOS ONE
Publisher:
Public Library of Science
Journal:
PLOS ONE
Issue Date:
22-Oct-2015
URI:
http://hdl.handle.net/10547/600878
DOI:
10.1371/journal.pone.0140483
Additional Links:
http://dx.plos.org/10.1371/journal.pone.0140483
Type:
Article
Language:
en
ISSN:
1932-6203
Sponsors:
This work was supported by Cancer Research U.K. (SEB, SAB)(http://www.cancerresearchuk.org/), a European Group for Blood and Marrow Transplant fellow (CL) (https://www.ebmt.org/Contents/Pages/Default.aspx), Leukaemia and Lymphoma Research (BG)(https://leukaemialymphomaresearch.org.uk/), Cork Cancer Research Centre (BG)(http://www.ccrc.ie/), Wellcome Value in People award (BG) (http://www.wellcome.ac.uk/Funding/Public-engagement/Funding-schemes/People-Awards-and-Society-Awards/), British Society for Haematology (BG) (http://www.b-s-h.org.uk/), the Wessex Cancer Trust (BG) (http://wessexcancer.org.uk/), and Research Foundation Flanders (ELS) (http://www.fwo.be/en/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Appears in Collections:
Biomedicine and Nutrition Research Group

Full metadata record

DC FieldValue Language
dc.contributor.authorBrooks, Suzanne E.en
dc.contributor.authorBonney, Stephanie A.en
dc.contributor.authorLee, Cindyen
dc.contributor.authorPublicover, Amyen
dc.contributor.authorKhan, Ghazalaen
dc.contributor.authorSmits, Evelien L.en
dc.contributor.authorSigurdardottir, Dagmaren
dc.contributor.authorArno, Matthewen
dc.contributor.authorLi, Deminen
dc.contributor.authorMills, Ken I.en
dc.contributor.authorPulford, Karenen
dc.contributor.authorBanham, Alison H.en
dc.contributor.authorvan Tendeloo, Viggoen
dc.contributor.authorMufti, Ghulam J.en
dc.contributor.authorRammensee, Hans-Georgen
dc.contributor.authorElliott, Tim J.en
dc.contributor.authorOrchard, Kim H.en
dc.contributor.authorGuinn, Barbara-Annen
dc.date.accessioned2016-03-08T11:17:45Zen
dc.date.available2016-03-08T11:17:45Zen
dc.date.issued2015-10-22en
dc.identifier.citationBrooks SE, Bonney SA, Lee C, Publicover A, Khan G, Smits EL, et al. (2015) Application of the pMHC Array to Characterise Tumour Antigen Specific T Cell Populations in Leukaemia Patients at Disease Diagnosis 2015, 10 (10):e0140483 PLOS ONEen
dc.identifier.issn1932-6203en
dc.identifier.doi10.1371/journal.pone.0140483en
dc.identifier.urihttp://hdl.handle.net/10547/600878en
dc.description.abstractImmunotherapy treatments for cancer are becoming increasingly successful, however to further improve our understanding of the T-cell recognition involved in effective responses and to encourage moves towards the development of personalised treatments for leukaemia immunotherapy, precise antigenic targets in individual patients have been identified. Cellular arrays using peptide-MHC (pMHC) tetramers allow the simultaneous detection of different antigen specific T-cell populations naturally circulating in patients and normal donors. We have developed the pMHC array to detect CD8+ T-cell populations in leukaemia patients that recognise epitopes within viral antigens (cytomegalovirus (CMV) and influenza (Flu)) and leukaemia antigens (including Per Arnt Sim domain 1 (PASD1), MelanA, Wilms’ Tumour (WT1) and tyrosinase). We show that the pMHC array is at least as sensitive as flow cytometry and has the potential to rapidly identify more than 40 specific T-cell populations in a small sample of T-cells (0.8–1.4 x 106). Fourteen of the twenty-six acute myeloid leukaemia (AML) patients analysed had T cells that recognised tumour antigen epitopes, and eight of these recognised PASD1 epitopes. Other tumour epitopes recognised were MelanA (n = 3), tyrosinase (n = 3) and WT1126-134 (n = 1). One of the seven acute lymphocytic leukaemia (ALL) patients analysed had T cells that recognised the MUC1950-958 epitope. In the future the pMHC array may be used provide point of care T-cell analyses, predict patient response to conventional therapy and direct personalised immunotherapy for patients.en
dc.description.sponsorshipThis work was supported by Cancer Research U.K. (SEB, SAB)(http://www.cancerresearchuk.org/), a European Group for Blood and Marrow Transplant fellow (CL) (https://www.ebmt.org/Contents/Pages/Default.aspx), Leukaemia and Lymphoma Research (BG)(https://leukaemialymphomaresearch.org.uk/), Cork Cancer Research Centre (BG)(http://www.ccrc.ie/), Wellcome Value in People award (BG) (http://www.wellcome.ac.uk/Funding/Public-engagement/Funding-schemes/People-Awards-and-Society-Awards/), British Society for Haematology (BG) (http://www.b-s-h.org.uk/), the Wessex Cancer Trust (BG) (http://wessexcancer.org.uk/), and Research Foundation Flanders (ELS) (http://www.fwo.be/en/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.en
dc.language.isoenen
dc.publisherPublic Library of Scienceen
dc.relation.urlhttp://dx.plos.org/10.1371/journal.pone.0140483en
dc.rightsArchived with thanks to PLOS ONEen
dc.subjectC550 Immunologyen
dc.subjectimmunotherapyen
dc.subjectpMHC arrayen
dc.subjectT-cellen
dc.subjectT cellen
dc.subjectleukaemiaen
dc.subjectleukaemia antigensen
dc.titleApplication of the pMHC array to characterise tumour antigen specific T cell populations in leukaemia patients at disease diagnosisen
dc.typeArticleen
dc.identifier.journalPLOS ONEen
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