Application of the pMHC array to characterise tumour antigen specific T cell populations in leukaemia patients at disease diagnosis
AuthorsBrooks, Suzanne E.
Bonney, Stephanie A.
Smits, Evelien L.J.
Mills, Ken I.
Banham, Alison H.
van Tendeloo, Viggo
Mufti, Ghulam J.
Elliott, Tim J.
Orchard, Kim H.
MetadataShow full item record
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.
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 ONE
PublisherPublic Library of Science
PubMed Central IDPMC4619595
SponsorsThis 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.
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