Professor Rutella is the Professor of Cancer Immunotherapy at the John van Geest Cancer Research Centre. He is a licensed haematologist with a long-standing clinical and research interest in cancer immunology and immunotherapy approaches for patients with leukaemia. At Nottingham Trent University, Professor Rutella’s research focuses on visualising the state of cancer-immune interactions in individual patients and on biomarker discovery, with the aim to guide treatment choices and improve clinical outcome.
Areas of clinical research interest for Professor Rutella’s team include:
- Novel immunotherapy approaches for haematological malignancies.
Elements of this research work focus on the challenges encountered with the effective treatment of acute myeloid leukaemia (AML) and combine systems biology approaches (targeted immune gene expression and micro-RNA profiling, spatially-resolved digital protein profiling-immunohistochemistry, multi-parameter flow cytometry, data mining and bioinformatics expertise) with AML patient-derived xenograft (PDX) models for preclinical testing of novel pharmaceutical agents to:
-Discover gene signatures that are reflective of general immune status and predictive of anti-cancer immune potential;
-Assess immune cell infiltration and the expression of immune checkpoint molecules;
-Identify ‘actionable’ molecular pathways that can predict patient outcome and therefore assist the tailoring and improve the effectiveness of therapeutic interventions.
- IFN-gamma-mediated tumour immune evasion and response to immunotherapy.
Pro-tumorigenic activities of IFN-gamma have recently emerged depending on the context, intensity and durability of IFN-gamma signalling. The research team is studying whether T-cell infiltration and IFN-gamma production in the AML bone marrow microenvironment correlate with patient response to immunotherapeutic agents, including novel bi-specific antibodies. Cutting-edge technologies, including spatially-resolved highly multiplex digital immunohistochemistry, are being used to analyse the location, density and functional orientation of the different immune cell populations in AML biopsies, i.e., the ‘immune contexture’ of the tumour microenvironment. We are also focusing on the role played by IFN-stimulated genes in mediating resistance of AML cells to chemotherapy agents.
- Analysis of high-dimensional transcriptomic data from human tumours.
We have obtained multiple data sets for AML, ovarian, prostate, lung and colorectal cancers from public repositories such as Array Express, TCGA and GEO. Inclusion in these studies is based on sample numbers (n>100) and good clinical annotation of samples (>95% complete coverage for 5 or more clinical features). Each data set is currently being mined for multiple immunological related features. The group has expertise in the identification of molecular features based on artificial neural network (ANN) analysis. We are also using analytical tools (CIBERSORT; PRECOG) to infer the frequency and quality of tumour-infiltrating immune cells from transcriptomic datasets and to identify immune determinants of patient response to therapy.
2014-2016: Executive Director of Clinical Research, Sidra Medical and Research Center, Doha, Qatar
2012-2014: Chair and Head of Service, Immunohaematology and Transfusion Medicine, Bambino Gesù Children’s Hospital, Rome, Italy
2000-2012: Assistant Professor of Haematology and Consultant Haematologist, Agostino Gemelli University Polyclinic, Catholic University Medical School, Rome, Italy
Areas of research interest include:
Discovery of predictive outcome biomarkers in cancer patients. Current work is focusing on the identification of specific gene signatures that reflect immune system activation, and help predict treatment response as well as risk of relapse in patients with cancer. Our NanoString FLEX instrument (one of only 6 in the UK) utilises a clinic-ready high-throughput platform with digital detection and direct molecular barcoding of individual target molecules. Specific proteins of interest are validated and quantified using Clinical Proteomics. All data analytic and interpretation activities are supported by advanced Bioinformatics and Computational Intelligence expertise.
Novel immunotherapy approaches for haematological malignancies. This research work tackles the immune suppressive circuits that prevent the establishment of effective anti-tumour responses in patients with acute leukaemia. The ultimate goal of these studies is to identify molecular pathways within the immunological tumour microenvironment that can be targeted in order to improve patient outcome. For instance, small molecule inhibitors of indoleamine 2,3-dioxygenase-1 (IDO1), an immune suppressive tryptophan-catabolising enzyme which is expressed in a subset of patients with acute myeloid leukaemia, are currently being used in patients with advanced-stage cancers.
Opportunities to carry out postgraduate research towards an MPhil/PhD exist within the School of Science and Technology and further information may be obtained from the NTU Doctoral School.
Fellow, Royal College of Pathologists, London, UK (2017)
- Full with Specialist Registration with a Licence to Practice (Haematology); ‘Ordine dei Medici Chirurghi e degli Odontoiatri’, Italy (reference number: 44979); from 10/06/1993
- Full with Specialist Registration with a Licence to Practice (Haematology); General Medical Council, United Kingdom (reference number: 7555758); from 06/01/2017
- Member of the American Society of Cell & Gene Therapy (2015-present)
- Member of the Biomarkers Task Force, Society for the Immunotherapy of Cancer (SITC), Bethesda, USA (2014-present)
- Member of the Society for Immunotherapy of Cancer (2011-present)
- Member of the American Association of Immunologists (1999-present)
- Member of the American Society of Haematology (1999-present)
- 2018, Medical Research Council/UK Research and Innovation – UKRI Future Leaders Fellowships, UK
- 2018, Science Foundation Ireland
- 2018, Newton International Fellowships, Academy of Medical Sciences, London, UK
- 2017, Deutsche Forschungsgemeinschaft (DFG), Bonn, Germany
- 2017, “Sparkathon” Fellowships, Society for Immunotherapy of Cancer, Bethesda, USA
- 2016, North West Cancer Research, United Kingdom
- 2016, Genentech Basic Fellowship, Society for Immunotherapy of Cancer (SITC), Bethesda, USA
- 2015, European Research Council (ERC) Starting Grants, Brussels
- 2014, STRATEGMED Program, National Centre for Research and Development, Warsaw, Poland
- 2013-2014, The Danish Council for Independent Research, Medical Sciences, Denmark
- 2013, Association for International Cancer Research (now Worldwide Cancer Research), Scotland, United Kingdom
- 2013, Leukaemia & Lymphoma Research ( now Bloodwise), United Kingdom
- 2013, French National Research Agency (ANR), Programme de Recherche Translationnelle en Santè (PRTS)
- 2012, The Netherlands Organization for Health Research and Development (ZonMw)
- 2012, Dutch Cancer Society, Amsterdam, The Netherlands
- 2011-present, Ministry of Education, University and Research, Italy
- 2010, Post-doctoral fellowships; Lise Meitner Program, Austrian Science Fund (FWF)
- 2010, Research Grants Council (RGC), Hong Kong
Sponsors and collaborators
Current research is being conducted with the collaboration of:
- Jan K. Davidson-Moncada, MD PhD, Director of Clinical Development and Research, MacroGenics Inc., Rockville, MD, USA
- Sarah K. Tasian, MD, Assistant Professor and PI – Leukaemia Biorepository, Division of Oncology, Children’s Hospital of Philadelphia, USA
- Marc Schmitz, MD, Professor of Immunology, University of Dresden, Germany
- Martin Bornhaeuser, MD, Professor of Haematology/Oncology, University of Dresden, Germany
- Barbara Seliger, PhD, Professor and Department Chair, Institute for Medical Immunology, Martin Luther University, Halle-Wittenberg, Germany
- Peter Oefner, Professor, Institute of Functional Genomics, University of Regensburg, Germany
- Alessandra Cesano, MD PhD, Chief Medical Officer, NanoString Technologies, Seattle, USA
Research funding includes:
- Immunological profiling of acute myeloid leukaemia, Roger Counter Foundation, Dorset, UK (2016-2019), £116,000
- Microenvironmental targets for restoring anti-tumour immunity in childhood acute leukaemia, Qatar National Research Fund (2016-2019), £598,000
- Alterations of A-to-I RNA editing in acute myeloid leukaemia, Italian Ministry of University and Scientific Research (2012-2014), £70,110
- Human mesenchymal stromal cells: Optimization of GMP-grade in vitro protocols as a pre-requisite for clinical application, Regione Lazio, Dipartimento Economico e Occupazionale (Lazio Region , Department of Economic and Occupational) (2013-2014), £346,500
- Molecular determinants of immune dysfunction in childhood leukaemia, Bambino Gesú Children’s Hospital (2012-2013), £84,520
- Indoleamine 2,3-dioxygenase 1 (IDO1) and immune suppression in human malignancies, Italian Ministry of University and Scientific Research (2011-2013), £39,730
- Hepatocyte growth factor and immune dysfunction in multiple myeloma, Italian Association for Cancer Research (2009-2012), £126,800
Adaptive immune gene signatures correlate with response to flotetuzumab, a CD123×CD3 bispecific DART® molecule, in patients with relapsed/refractory acute myeloid leukemia. Rutella S, Church SE, Vadakekolathu J, Viboch E, Sullivan AH, Hood T, Warren SE, Cesano A, LaMotte-Mohs R, Muth J, Lelievre H, Löwenberg B, DiPersio JF, Davidson-Moncada JK. Blood 2018 132: 444; DOI: https://doi.org/10.1182/blood-2018-99-111539.
Neutrophils kill antibody-opsonized cancer cells by trogoptosis. Matlung HL, Babes L, Zhao XW, van Houdt M, Treffers LW, van Rees DJ, Katka Franke K, Schornagel K, Verkuijlen P, Janssen H, Halonen P, Lieftink C, Beijersbergen RL, Leusen JHW, Boelens JJ, Kuhnle I, van der Werff Ten Bosch J, Seeger K, Rutella S, Pagliara D, Matozaki T, Suzuki E, Menke-van der Houven van Oordt CW, van Bruggen R, Roos D, van Lier RAW, Kuijpers TW, Kubes P, van den Berg TK. Cell Reports 2018; 23: 3946-59.
Systematic evaluation of immune regulation and modulation. Stroncek DF, Butterfield LH, Cannarile MA, Dhodapkar MV, Greten TF, Grivel JC, Kaufman DR, Kong HH, Korangy F, Lee PP, Marincola F, Rutella S, Siebert JC, Trinchieri G, Seliger B. Journal for Immunotherapy of Cancer 2017; 5: 21.
Mesenchymal stem cells reduce colitis in mice via release of TSG6, independently of their localization to the intestine. Sala E, Genua M, Petti L, Anselmo A, Arena V, Cibella J, Zanotti L, D’Alessio S, Scaldaferri F, Luca G, Arato I, Calafiore R, Sgambato A, Rutella S, Locati M, Danese S and Vetrano S, Gastroenterology, 2015, 149 (1), 163-76
The urokinase plasminogen activator receptor (uPAR) controls macrophage phagocytosis in intestinal inflammation. Genua M, D’Alessio S, Cibella J, Gandelli A, Sala E, Correale C, Arena V, Malesci A, Rutella S, Ploplis VA, Vetrano S, and Danese S, Gut, 2015, 64 (4), 589-600
Indoleamine 2,3-dioxygenase 1 (IDO1) activity in leukemia blasts correlates with poor outcome in childhood acute myeloid leukemia. Folgiero V, Goffredo BM, Filippini P, Masetti R, Bonanno G, Caruso R, Bertaina V, Mastronuzzi A, Gaspari S, Zecca M, Torelli GF, Testi AM, Pession A, Locatelli F, and Rutella S, Oncotarget, 2014, 5 (8), 2052-64
Kindlin-3-independent adhesion of neutrophils from leukocyte adhesion deficiency type III. van de Vijver E, Tool ATJ, Sanal O, Cetin M, Unal S, Aytac S, Seeger K, Pagliara D, Rutella S, van den Berg TK and Kuijpers TW, Journal of Allergy and Clinical Immunology, 2014, 133 (4), 1215-18
HLA-haploidentical stem cell transplantation after removal of αβ+ T and B cells in children with non-malignant disorders. Bertaina A, Merli P, Rutella S, Pagliara D, Bernardo ME, Masetti R, Pende D, Falco ME, Handgretinger R, Moretta F, Lucarelli B, Brescia LP, Li Pira G, Testi M, Cancrini C, Kabbara N, Carsetti R, Finocchi A, Moretta A, Moretta L, Locatelli F, Blood, 2014, 124 (5), 822-6
Bacterial sensor triggering receptor expressed on myeloid cells-2 regulates the mucosal inflammatory response. Correale C, Genua M, Vetrano S, Mazzini E, Martinoli C, Spinelli A, Arena V, Peyrin-Biroulet L, Caprioli F, Passini N, Panina-Bordignon P, Repici A, Malesci A, Rutella S, Rescigno M, and Danese S, Gastroenterology, 2013, 144 (2), 346-56
Results of the AIEOP AML 2002/01 multicenter, prospective trial for treatment of children with acute myeloid leukemia. Pession A, Masetti R, Rizzari C, Putti MC, Casale F, Fagioli F, Luciani M, Lo Nigro L, Menna G, Micalizzi C, Santoro N, Testi AM, Zecca M, Biondi A, Pigazzi M, Rutella S, Rondelli R, Basso G, and Locatelli F, Blood, 2013, 122 (2) 170-8
How I treat relapsed childhood acute lymphoblastic leukemia. Locatelli F, Schrappe M, Bernardo ME, and Rutella S, Blood, 2012, 120 (14), 2807-16See all of Sergio Rutella's publications...
- Haematological cancers
- Immunotherapy (harnessing the immune system to fight cancer)
- Personalised cancer medicine
- Cancer genomics