Sergio_Rutella

Sergio Rutella

Professor

School of Science & Technology

Role

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:

  1. 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.

  2. 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.

  3. 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.

Career overview

2016-present: Professor of Cancer Immunotherapy and Research Coordinator for Biosciences, John van Geest Cancer Research Centre, School of Science and Technology, Nottingham Trent University, Nottingham, United Kingdom

2017: Fellow of the Royal College of Pathologists, United Kingdom

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

2011: Consultant Haematologist, Department of Paediatric Haematology/Oncology and Transfusion Medicine, Bambino Gesù Children’s Hospital, Rome, Italy

2000-2011: Assistant Professor of Haematology and Consultant Haematologist, Agostino Gemelli University Polyclinic, Catholic University Medical School, Rome, Italy

2001 (1997-2001): PhD in Experimental Haematology, Catholic University Medical School, Rome, Italy

1997 (1993-1997): Post-graduate specialisation (Certificate of Completion of Training) in Haematology (summa cum laude), Catholic University Medical School, Rome, Italy

1993 (1986-1993): Degree in Medicine and Surgery (MD; summa cum laude), Catholic University Medical School, Rome, Italy

Honours and international recognition:

2019: Vice Chancellor's Outstanding Researcher Award (Established Researcher), Nottingham Trent University, United Kingdom

2011: Junior Faculty Award, American Association of Immunologists, Bethesda, MD, USA

2006: Junior Faculty Award, American Association of Immunologists, Bethesda, MD, USA

2005: European Commission’s Marie Curie Actions Scholarship, ESH-EBMT Eurocord

2003: Showell-Pfizer Award, American Association of Immunologists, Bethesda, MD, USA

2002: Showell-Pfizer Award, American Association of Immunologists, Bethesda, MD, USA

Research areas

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.

External activity

Scientific advisory boards, research grants and personal fellowship schemes

2019-Health and Care Research Wales, United Kingdom

2019-Breast Cancer Now, London, United Kingdom

2019 -The Netherlands Organization for Health Research and Development (ZonMw)

2019-Scientific Advisory Board, Institute for Advanced Biosciences (IAB), Grenoble, France

2018-Medical Research Council/UK Research and Innovation – UKRI Future Leaders Fellowships

2018-Science Foundation Ireland – SFI Career Development Award and Site Review, Dublin

2018-Newton International Fellowships, Academy of Medical Sciences, London, UK

2017-Scientific Advisory Board, Collaborative Research Centre Programme, Deutsche Forschungsgemeinschaft (DFG), Bonn, Germany

2017-“Sparkathon” Fellowship (https://www.sitcancer.org/education/sparkathon), Society for Immunotherapy of Cancer (SITC), Bethesda, MD, USA

2017-Biomedicines Travel Award, Selection Committee Member, MDPI Publisher, Basel, Switzerland

2016-North West Cancer Research, UK

2016-Genentech Basic Fellowship, Society for Immunotherapy of Cancer (SITC), Bethesda, MD, USA

2015-European Research Council (ERC) Starting Grants, Brussels

2014-STRATEGMED Program, National Centre for Research and Development, Warsaw, Poland

2014-The Danish Council for Independent Research | Medical Sciences, Denmark

2013-Association for International Cancer Research (AICR), Scotland, United Kingdom

2013-Leukaemia & Lymphoma Research (LLR), 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-San Raffaele University, Milan, Italy

2011-Young Researcher schemes (FIRB), 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:

Research funding includes

  • Identification of prognostic/predictive immune gene signatures in patients with relapsed/refractory acute myeloid leukaemia receiving flotetuzumab immunotherapy. MacroGenics, Inc., Rockville, United States of America and NanoString Technologies, Inc., Seattle, United States of America
  • Identification of prognostic/predictive immune gene signatures in patients with advanced gastric cancer receiving immunotherapy with pembrolizumab and anti-HER2 antibodies. MacroGenics, Inc., Rockville, United States of America and NanoString Technologies, Inc., Seattle, United States of America
  • Tipifarnib and interferon signalling in acute myeloid leukaemia. Kura Oncology, San Diego, United States of America
  • 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 (PRIN; 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 (PRIN; 2011-2013), £39,730
  • Hepatocyte growth factor and immune dysfunction in multiple myeloma, Italian Association for Cancer Research (2009-2012), £126,800

Publications

During his academic career, Professor Sergio Rutella has authored and co-authored 209 full-length, peer-reviewed publications (H-index=52; i10-index=158; times cited=9,380) and 13 book chapters, and has secured £4,122,718 of research funding as principal investigator/co-investigator.

A parsimonious 3-gene signature predicts clinical outcomes in an acute myeloid leukemia multicohort study. Wagner S, Vadakekolathu J, Tasian SK, Altmann H, Bornhäuser M, Pockley AG, Ball GR, Rutella S. Blood Adv. 2019 Apr 23;3(8):1330-1346. doi: 10.1182/bloodadvances.2018030726.

Phase 1 cohort expansion of flotetuzumab, a CD123×CD3 bispecific Dart® protein in patients with relapsed/refractory acute myeloid leukemia (AML). Uy GL, Rettig MP, Vey N, Godwin J, Foster MC, Rizzieri DA, Arellano ML, Topp MS, Huls G, Jongen-Lavrencic M, Martinelli G, Paolini S, Ciceri F, Carrabba MG, Sweet KL, Ravandi, Church SE, Vadakekolathu J, Rutella S, Sun J, Yang K, Baughman J, Curtis T, Timmeny E, Cali K, Tran K, Muth J, La Motte-Mohs R, Poirot C, Pallis A, Cesano A, Bonvini E, Wigginton J, Lowenberg B, Davidson-Moncada JK, DiPersio J.F. Blood. 2018 132:764; doi: https://doi.org/10.1182/blood-2018-99-117085

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 Rep. 2018 Jun 26;23(13):3946-3959.e6. doi: 10.1016/j.celrep.2018.05.082.

Capturing the complexity of the immune microenvironment of acute myeloid leukemia with 3D biology technology. Rutella S, Vadakekolathu J, Patel T, Reeder S, Schmitz M, Schaarschmidt H, Warren SE, Liang Y, Hood T, Danaher P, Cesano A, Beechem JM, Pockley AG, Tasian SK, Bornhäuser M. J Clin Oncol. 2018; 36 (Suppl. 5S; A#50). doi: 10.1200/JCO.2018.36.5_suppl.50.

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. J Immunother Cancer. 2017 Mar 21;5:21. doi: 10.1186/s40425-017-0223-8.

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 Jul;149(1):163-176.e20. doi: 10.1053/j.gastro.2015.03.013.

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 Apr;64(4):589-600. doi: 10.1136/gutjnl-2013-305933.

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. J Allergy Clin Immunol. 2014 Apr;133(4):1215-8. doi: 10.1016/j.jaci.2013.10.020.

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, Danese S. Gastroenterology. 2013 Feb;144(2):346-356.e3. doi: 10.1053/j.gastro.2012.10.040.

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 Jul 11;122(2):170-8. doi: 10.1182/blood-2013-03-491621.

Hematopoietic stem cell transplantation for children with high-risk acute lymphoblastic leukemia in first complete remission: a report from the AIEOP registry. Fagioli F, Quarello P, Zecca M, Lanino E, Rognoni C, Balduzzi A, Messina C, Favre C, Foà R, Ripaldi M, Rutella S, Basso G, Prete A, Locatelli F. Haematologica. 2013 Aug;98(8):1273-81. doi: 10.3324/haematol.2012.079707.

How I treat relapsed childhood acute lymphoblastic leukemia. Locatelli F, Schrappe M, Bernardo ME, Rutella S. Blood. 2012 Oct 4;120(14):2807-16. doi: 10.1182/blood-2012-02-265884.

Indoleamine 2,3-dioxygenase-expressing leukemic dendritic cells impair a leukemia-specific immune response by inducing potent T regulatory cells. Curti A, Trabanelli S, Onofri C, Aluigi M, Salvestrini V, Ocadlikova D, Evangelisti C, Rutella S, De Cristofaro R, Ottaviani E, Baccarani M, Lemoli RM. Haematologica. 2010 Dec;95(12):2022-30. doi: 10.3324/haematol.2010.025924.

Cells with characteristics of cancer stem/progenitor cells express the CD133 antigen in human endometrial tumors. Rutella S, Bonanno G, Procoli A, Mariotti A, Corallo M, Prisco MG, Eramo A, Napoletano C, Gallo D, Perillo A, Nuti M, Pierelli L, Testa U, Scambia G, Ferrandina G. Clin Cancer Res. 2009 Jul 1;15(13):4299-311. doi: 10.1158/1078-0432.CCR-08-1883.

Critical role of the CD40 CD40-ligand pathway in regulating mucosal inflammation-driven angiogenesis in inflammatory bowel disease. Danese S, Scaldaferri F, Vetrano S, Stefanelli T, Graziani C, Repici A, Ricci R, Straface G, Sgambato A, Malesci A, Fiocchi C, Rutella S. Gut. 2007 Sep;56(9):1248-56.

Modulation of tryptophan catabolism by human leukemic cells results in the conversion of CD25- into CD25+ T regulatory cells. Curti A, Pandolfi S, Valzasina B, Aluigi M, Isidori A, Ferri E, Salvestrini V, Bonanno G, Rutella S, Durelli I, Horenstein AL, Fiore F, Massaia M, Colombo MP, Baccarani M, Lemoli RM. Blood. 2007 Apr 1;109(7):2871-7.

MyoD expression restores defective myogenic differentiation of human mesoangioblasts from inclusion-body myositis muscle. Morosetti R, Mirabella M, Gliubizzi C, Broccolini A, De Angelis L, Tagliafico E, Sampaolesi M, Gidaro T, Papacci M, Roncaglia E, Rutella S, Ferrari S, Tonali PA, Ricci E, Cossu G. Proc Natl Acad Sci U S A. 2006 Nov 7;103(45):16995-7000.

Tolerogenic dendritic cells: cytokine modulation comes of age. Rutella S, Danese S, Leone G. Blood. 2006 Sep 1;108(5):1435-40.

Hepatocyte growth factor favors monocyte differentiation into regulatory interleukin (IL)-10++IL-12low/neg accessory cells with dendritic-cell features. Rutella S, Bonanno G, Procoli A, Mariotti A, de Ritis DG, Curti A, Danese S, Pessina G, Pandolfi S, Natoni F, Di Febo A, Scambia G, Manfredini R, Salati S, Ferrari S, Pierelli L, Leone G, Lemoli RM. Blood. 2006 Jul 1;108(1):218-27.

Mobilization of bone marrow-derived stem cells after myocardial infarction and left ventricular function. Leone AM, Rutella S, Bonanno G, Abbate A, Rebuzzi AG, Giovannini S, Lombardi M, Galiuto L, Liuzzo G, Andreotti F, Lanza GA, Contemi AM, Leone G, Crea F. Eur Heart J. 2005 Jun;26(12):1196-204.

Negative prognostic value of glutathione S-transferase (GSTM1 and GSTT1) deletions in adult acute myeloid leukemia. Voso MT, D'Alo' F, Putzulu R, Mele L, Scardocci A, Chiusolo P, Latagliata R, Lo-Coco F, Rutella S, Pagano L, Hohaus S, Leone G. Blood. 2002 Oct 15;100(8):2703-7.

Role for granulocyte colony-stimulating factor in the generation of human T regulatory type 1 cells. Rutella S, Pierelli L, Bonanno G, Sica S, Ameglio F, Capoluongo E, Mariotti A, Scambia G, d'Onofrio G, Leone G. Blood. 2002 Oct 1;100(7):2562-71.

Expression of the c-met proto-oncogene and its ligand, hepatocyte growth factor, in Hodgkin disease. Teofili L, Di Febo AL, Pierconti F, Maggiano N, Bendandi M, Rutella S, Cingolani A, Di Renzo N, Musto P, Pileri S, Leone G, Larocca LM. Blood. 2001 Feb 15;97(4):1063-9.

Modulation of bcl-2 and p27 in human primitive proliferating hematopoietic progenitors by autocrine TGF-beta1 is a cell cycle-independent effect and influences their hematopoietic potential. Pierelli L, Marone M, Bonanno G, Mozzetti S, Rutella S, Morosetti R, Rumi C, Mancuso S, Leone G, Scambia G. Blood. 2000 May 15;95(10):3001-9.

Effect of all-trans retinoic acid on procoagulant and fibrinolytic activities of cultured blast cells from patients with acute promyelocytic leukemia. De Stefano V, Teofili L, Sica S, Mastrangelo S, Di Mario A, Rutella S, Salutari P, Rumi C, d'Onofrio G, Leone G. Blood. 1995 Nov 1;86(9):3535-41.

Autologous stem cell transplantation: release of early and late acting growth factors relates with hematopoietic ablation and recovery. Testa U, Martucci R, Rutella S, Scambia G, Sica S, Benedetti Panici P, Pierelli L, Menichella G, Leone G, Mancuso S, et al. Blood. 1994 Nov 15;84(10):3532-9.

See all of Sergio Rutella's publications...

Press expertise

  • Haematological cancers
  • Leukaemia
  • Immunotherapy (harnessing the immune system to fight cancer)
  • Personalised cancer medicine
  • Cancer genomics