Our research has two main streams: immunohistochemical screening and microscope-based assays.
1. Immunohistochemical screening
We focus on high throughput immunohistochemical screening and characterization of molecules involved in various cellular pathways in order to identify novel diagnostic, therapeutic and prognostic markers. This has allowed identification of novel diagnostic markers for haematological malignancies (and solid tumours), and it served as an enabling methodology for basic translational research cutting across various research themes and landing to collaborations within academia and industry, locally, nationally and internationally.
2. Microscope-based assays
The second arm of our research activity is to develop microscope-based assays such as the Recently established multiplex immunolabelling (MIL) technique that can be applied on diagnostic FFPE and fluid samples to characterise in depth the phenotype of tumour cells as well as to analyse the tumour microenvironment. At UCL Cancer Institute, in collaboration with several research teams this technology has been largely used to study intratumour heterogeneity of T-cell clones in a variety of tumours and to monitor resistance to therapy. One of these studies has been successfully published in Science: McGranahan N. et al. Clonal neoantigens elicit T cell immunoreactivity and sensitivity to immune checkpoint blockade. Science 2016 Mar 3; 1490.
Research developments
In progress is the development of a “superplex” immunostaining for detection of up 7 proteins in tissue samples. The assay has been established by Ayse Akarca, the senior member of the team.
Additional techniques in use in our team include: a) multispectral immunofluorescence technique based upon the VECTRA system that allows the simultaneous detection of several molecules in tissue sections. This methodology is useful to quantify cell subsets and proteins co-localisation; b) BASE and RNAscope technology, a sensitive approach for RNA in situ hybridization, that enables multiplex fluorescent and chromogenic detection and quantification of RNA biomarkers.
The team provides service for Multiplex immunolabelling to pharmaceutical companies and clinical trials.
Selected publications
- Schmidt J, Gong S, Marafioti T, Mankel B, et al. Genome-wide analysis of pediatric-type follicular lymphoma reveals low genetic complexity and recurrent alterations of TNFRSF14 gene. Blood, 128:1101-11; 2016
- McGranahan, Furness AJS, Rosenthal R ... Marafioti T et al. Clonal neoantigens elicit T cell immunoreactivity and sensitivity to immune checkpoint. Science, 351(6280):1463-9; 2016
- Llibre A, López-Macías C, Marafioti T, Mehta H, et al. LLT1 and CD161 expression in human germinal centers promotes B cell activation and CXCR4 downregulation. J. Immunol, 196(5):2085-94; 2016
- Sellar RS, Fend F, Akarca A ... Marafioti T. BRAFV600E mutations are found in Richter syndrome and may allow targeted therapy in a subset of patients. Br J Haematol, 170:282-5; 2015.
- Agostinelli C, Rizvi H, Paterson J ... Marafioti T. Intracellular TCR-signalling pathway: novel markers for lymphoma diagnosis and potential therapeutic targets. Am J Surg Pathol , 1349-59; 2014.
- Rimsza LM, Day WA, McGinn S ... Marafioti T, Grogan TM. Kappa and lambda light chain mRNA in situ hybridization compared to flow cytometry and immunohistochemistry in B cell lymphomas. Diagn Pathol, 21:144; 2014
- Marafioti T, Copie-Bergman C, Calaminici M, Paterson JC, et al. Another look at follicular lymphoma: immunophenotypic and molecular analyses identify distinct follicular lymphoma subgroups. Histopathology, 62:860-75; 2013
- Akarca AU, Shende VH, Ramsay AD ... Marafioti T. BRAF V600E mutation-specific antibody, a sensitive diagnostic marker revealing minimal residual disease in hairy cell leukaemia. Br J Haematol, 162:848-51; 2013
- Moroch J, Copie-Bergman C, de Leval L ... Marafioti T, Gaulard P. Follicular peripheral T-cell lymphoma expands the spectrum of classical Hodgkin lymphoma mimics. Am J Surg Pathol, 36:1636-46; 2012
- Agostinelli C, Paterson JC, Gupta R ... Marafioti T. Detection of LIM domain only 2 (LMO2) in normal human tissues and haematopoietic and non-haematopoietic tumours using a newly developed rabbit monoclonal antibody. Histopathology, 61:33-46; 2012.