Immune-onco Pathology

Group leader: Dr Teresa Marafioti 

Research 

Our research has two main streams:

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 last year - Clonal neoantigens elicit T cell immunoreactivity and sensitivity to immune checkpoint blockade. McGranahan N et al. 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. Contact: Ayse Akarca a.akarca@ucl.ac.uk.

Selected publications

1. Schmidt J, Gong S, Marafioti T, Mankel B, Gonzalez-Farre B, Balagué O, Mozos A, Cabeçadas J, van der Walt J, Hoehn D, Rosenwald A, Ott G, Dojcinov S, Egan C, Nadeu F, Ramis-Zaldívar JE, Clot G, Bárcena C, Pérez-Alonso V, Endris V, Penzel R, Lome-Maldonado C, Bonzheim I, Fend F, Campo E, Jaffe ES, Salaverria I, Quintanilla-Martinez L. Genome-wide analysis of pediatric-type follicular lymphoma reveals low genetic complexity and recurrent alterations of TNFRSF14 gene. Blood, 128:1101-11; 2016
2. McGranahan,  Furness AJS, Rosenthal R,Ramskov, S, Lyngaa R, Saini SK, Jamal-Hanjani M, Wilson GA , Birkbak1 NJ ,Hiley CT, Watkins TBK,  Shafih S, Murugaesu N, Richard Mitter R, Akarca AU , Linares J, Marafioti T , Jake Y. Henry JY, Van Allen EM, Miao D,  Schilling B, Schadendorf D, Levi Garraway L,  Makarov V, Rizvi NA, Snyder A, Hellmann MD, Merghoub T, Wolchok JD,Shukla SA, , Catherine J. Wu, Peggs KS, Chan TA ,Hadrup, SR, Sergio A. Quezada SA, Swanton C. Clonal neoantigens elicit T cell immunoreactivity and sensitivity to immune checkpoint. Science, 351(6280):1463-9; 2016 
3. Llibre A, López-Macías C, Marafioti T, Mehta H, Partridge A, Kanzig C, Rivellese F, Galson JD, Walker LJ|, Milne P, Phillips RE, Kelly DF, Freeman GJ, El Shikh MEM, Klenerman P, Willberg CB. LLT1 and CD161 expression in human germinal centers promotes B cell activation and CXCR4 downregulation. J. Immunol, 196(5):2085-94; 2016 
4. Sellar RS, Fend F, Akarca A, Agostinelli C, Shende V, Quintanilla-Martínez L, Stein H, Pileri SA, Linch D, 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.
5. Agostinelli C, Rizvi H,  Paterson J, Shende V, Akarca AU  Agostini E, Fuligni F, Righi S, Spagnolo S, Piccaluga PP, Pileri SA, Marafioti T. Intracellular TCR-signalling pathway: novel markers for lymphoma diagnosis and potential therapeutic targets. Am J Surg Pathol , 1349-59; 2014
6. Rimsza LM, Day WA, McGinn S, Pedata A, Natkunam Y, Warnke R, Cook JR, 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 
7. Marafioti T, Copie-Bergman C, Calaminici M, Paterson JC, Shende VH, Liu H, Baia M, Ramsay AD, Agostinelli C, Brière J, Clear A, Du MQ, Piccaluga PP, Masir N, Nacheva EP, Sujobert P, Shanmugam K, Grogan TM, Brooks SP, Khwaja A, Ardeshna K, Townsend W, Pileri SA, Haioun C, Linch D, Gribben JG, Gaulard P, Isaacson PG. Another look at follicular lymphoma: immunophenotypic and molecular analyses identify distinct follicular lymphoma subgroups. Histopathology, 62:860-75; 2013  
8. Akarca AU, Shende VH, Ramsay AD, Diss T, Pane-Foix M, Rizvi H, Calaminici MR, Grogan TM, Linch D, 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 
9. Moroch J, Copie-Bergman C, de Leval L, Plonquet A, Martin-Garcia N, Delfau- Larue M-H, Molinier-Frenkel V, Belhadj K, Haioun C, Audouin J, Swerdlow SH, 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
10. Agostinelli C, Paterson JC, Gupta R, Righi S, Sandri F, Piccaluga PP, Bacci F, Sabattini E, Pileri SA, 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.