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Sergio_Rutella

Sergio Rutella

Professor and Director of the John van Geest Cancer Research Centre

School of Science & Technology

Role

Professor Sergio Rutella, MD PhD, is a licensed haematologist and Fellow of the Royal College of Pathologists (FRCPath). He received NTU’s Vice Chancellor’s Outstanding Researcher Award in 2019 and has been elected as a Fellow by the Royal Society of Biology on 1 April 2022 for "Haematology work and impact on the Biosciences".

Professor Rutella is the current Director of the John van Geest Cancer Research Centre at Nottingham Trent University.  His academic career has been predicated on the bench-to-bedside-to-bench paradigm in Haematology. Over the last 25 years, Professor Rutella has been engaged in clinical and translational research focusing on immunotherapy approaches to improve the outcome of haematological malignancies, with an emphasis on antibody-based therapeutics and haematopoietic stem cell processing and transplantation. He has an extensive track record of leading studies that involve a strong correlative component and collaborating with other investigators, both basic and clinical.

At Nottingham Trent University, Professor Rutella’s translational research program focuses on deciphering the immune ecosystems of haematological malignancies, on visualising the state of cancer-immune interactions in individual patients and on biomarker discovery, with the aim to implement the design of rational immunotherapy approaches, guide treatment choices and minimise toxicity. We nurture the ambition to help design immunotherapy clinical trials that select cancer patients based on immune states and markers, and to test whether this strategy increases the rate of durable responses.

During his academic career, Professor Rutella has authored and co-authored 223 full-length, peer-reviewed publications (H-index = 60; i10-index = 180; times cited > 12,500; total impact factor = 1,758.733) and 13 book chapters, and has secured £5,356,754 of research funding as principal investigator/co-investigator. His teaching contributions are made to Bachelors and Masters projects on the BIOL40111 MSc Research Project module, the BIOL40102 "Research Methods and Bioethics" module, and the BIOL33171 "Immunology and Virology" module

Professor Rutella has led a REF2021 Impact Case Study titled: ‘Improving the Management and Survival of Patients with Aggressive, Treatment-Resistant Cancers’ (https://www.ntu.ac.uk/research/impact-case-studies/ref-2021/improving-the-management-and-survival-of-patients-with-aggressive,-treatment-resistant-cancers).

Career overview

2022 (April): Elected as a Fellow by the Royal Society of Biology for his "Haematology work and impact on the Biosciences"

2021 (April)-present: Director, John van Geest Cancer Research Centre, Nottingham Trent University, Nottingham, United Kingdom

2020 (Oct)-2021 (March): Interim Director, John van Geest Cancer Research Centre, Nottingham Trent University, Nottingham, United Kingdom

2020 (Jan)-2022 (May): Inaugural Director, Centre for Health, Ageing and Understanding Disease (CHAUD), School of Science and Technology, Nottingham Trent University, Nottingham, United Kingdom

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

2017: Fellowship by Published Works; Royal College of Pathologists, United Kingdom

2017: General Medical Council (GMC) Specialist Registration (Haematology) with a Licence to Practice, United Kingdom (GMC reference no: 7555758)

2014-2016: Executive Director of Clinical Research, Sidra Medical and Research Center, Doha, Qatar

2012-2014: Chair and Head of Clinical 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: Full Registration with a Licence to Practice, Italian Regulatory Authority for Physicians and Dentists (Ordine dei Medici Chirurghi e degli Odontoiatri; License n. 44979; http://www1.ordinemediciroma.it)

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 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 RNA/protein profiling (GeoMx DSP), multi-parameter flow cytometry, computational immunology and bioinformatics expertise) 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’ targets/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 bispecific antibodies and chimeric antigen receptor (CAR) T cells. Cutting-edge technologies, such as GeoMx-DSP and single-cell RNA-sequencing, are being used to analyse the location, density and functional orientation of the different immune cell populations in primary tissue 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 curated publicly available datasets for AML, melanoma, ovarian, prostate, lung and colorectal cancers. Each data set is currently being mined for multiple cancer-related features, including signatures of immune effector senescence. The group has expertise in the identification of molecular drivers of cancer phenotypes based on artificial neural network (ANN) analysis. We are also using immune deconvolution algorithms (CIBERSORT; PRECOG; EPIC; quanTIseq) to infer the frequency and quality of tumour-infiltrating immune cells from transcriptomic datasets and to identify immune determinants of patient response to therapy.

Pharmacological re-activation of mutant TP53 in acute myeloid leukaemia and its effect on the expression of inflammatory mediators.

TP53-mutated human malignancies, including AML, are characterised by chemotherapy resistance and a poor clinical outcome. The great majority of TP53 mutations in AML are associated with loss-of-function (LOF) of the mutated protein. The team have generated data showing that TP53 mutations correlate with the expression of inflammatory molecules in the tumour microenvironment. This element of work aims to understand how the pharmacological re-activation of TP53 affects the expression of inflammatory genes in AML cells, with a focus on interferon-inducible molecules and on actionable  immune checkpoints. We use state-of-the-art gene expression profiling and proteomics platforms, as well as conventional cellular and molecular immunology techniques, to interrogate the immune transcriptome and proteome of AML cells bearing common TP53 mutations, also dissecting the interplay between TP53 and STAT1, a key interferon-stimulated gene. The following link provides media coverage to some of the ongoing research in this area (2019 SITC Annual Meeting, National Harbor, MD, USA):

https://www.mdedge.com/hematology-oncology/article/212531/aml/will-tp53-mutated-aml-respond-immunotherapy

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, invited talks and other indicators of esteem

2023-Invited Faculty, 6th International Conference "Acute myeloid leukaemia 'molecular and translational': advances in biology and treatment" (October 29-31, 2023; Estoril, Portugal)

28-30 June 2023: Immunotherapy for TP53-mutated AML. Advances in Stem cell Transplantation and Cell Therapy Symposium, Albert-Ludwigs-Universität Freiburg, Germany (Host: Professor Dr Robert Zeiser)

8-9 July 2022: Immune effector senescence and treatment response in acute myeloid leukaemia. Tumour Immunology Meets Oncology (TIMO) XVI Meeting, Martin Luther University, Halle-Wittenberg, Germany (Host: Professor Dr Barbara Seliger)

2022-Invited Faculty, European Haematology Association Thematic Days on "Emerging new therapies for AML" (June 15-17, 2022)

2022-Scientific Advisory Board, Collaborative Research Centre Programme, Deutsche Forschungsgemeinschaft (DFG), Bonn, Germany

31 March 2022-Invited Faculty, Korean Society of Hematology International Conference & 64th Annual Meeting (Immune landscapes and chemotherapy resistance in AML), Seoul, South Korea (ICKSH 2022)

2021-Invited Faculty, Scientific Committee on Myeloid Neoplasia (Immune evasion and immunotherapy in myeloid malignancies), 63rd American Society of Hematology (ASH) Meeting (Atlanta, USA; 11-14 December 2021).

2021-Invited Faculty, ESMO Immuno-Oncology Meeting's Educational Program (Understanding the microenvironment of haematological malignancies to overcome immune resistance), 8-11 December 2021, Geneva, Switzerland.

2021-Scientific Advisory Board, Advanced Clinician Scientist Programme CAMINO - "Career Advancement in Multidimensional Tumour Targeting", Technische Universität Dresden, Dresden, Germany (Professor Dr. Martin Bornhäuser).

2021-Ministry of Health, Singapore (Clinician Scientist - Individual Research Grant Scheme)

2021-Medical Research Council, UK (Clinical Academic Research Partnerships Scheme)

2021-Scientific Advisory Board, Collaborative Research Centre Programme, Deutsche Forschungsgemeinschaft (DFG), Bonn, Germany

2020-Invited Faculty, Meet-the-expert, Society for Immunotherapy of Cancer (SITC) Annual Meeting, National Harbor, MD, USA (11-14 November 2020).

2020-Selection Committee, Gottfried Wilhelm Leibniz Prize, Deutsche Forschungsgemeinschaft (DFG), Germany

2020-National Institute for Health Research (NIHR), UK

2020-Innovation and Technology Commission (ITC), Government of Hong Kong

2020-Medical Research Council, UK (New Investigator Research Grant, NIRG; Infections and Immunity Board)

2020-Medical Research Council, UK (Research Grant, Molecular & Cellular Medicine Board)

2020-Irish Cancer Society - Translational Research Fellowship Scheme

2020-Section Editor-In-Chief (Haematology), Journal of Clinical Medicine (IF 5.688)

2019-Fondazione Cariplo, Milan, Italy

2019-King Abdullah International Medical Research Centre (KAIMRC), Saudi Arabia

2019-Prostate Research Cancer Centre, London, United Kingdom

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-Co-Chair, Clinical & Biomarker Data Sharing Subcommittee, Society for Immunotherapy of Cancer, USA

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-Deputy Chair, Human Ethics Committee, School of Science and Technology, Nottingham Trent University, 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), USA

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

2016-2018-Institutional Review Board; Alternate Member; Sidra Medical & Research Centre, Doha, Qatar

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-Member, Biomarkers Task Force (WG3), Society for the Immunotherapy of Cancer (SITC), USA

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

Media Coverage

Professor Rutella has appeared in several newspaper/media articles. To read the stories, please follow the links below.

  • February 2022                        Research reimagined, https://www.ntu.ac.uk/research/research-reimagined/repair
  • March 2021                             https://www.ntu.ac.uk/about-us/news/news-articles/2021/03/john-van-geest-cancer-research-fundinguary 200
  • December 2020                      http://ir.macrogenics.com/news-releases/news-release-details/macrogenics-presents-flotetuzumab-data-patients-refractory-acute
  • October 2020                          https://www.macrogenics.com/news/macrogenics-announces-flotetuzumab-publication-in-blood-advances/
  • September 2020                     http://ir.macrogenics.com/news-releases/news-release-details/macrogenics-announces-publication-flotetuzumab-interim-phase-12
  • June 2020                               https://www.precisiononcologynews.com/cancer/gene-expression-signature-may-predict-chemo-resistance-immunotherapy-response-aml-patients#.XvxvnxP0lGw
  • June 2020                               https://medicalxpress.com/news/2020-06-paves-faster-accurate-therapies-hard-to-treat.html
  • June 2020                               http://ir.macrogenics.com/news-releases/news-release-details/macrogenics-announces-publication-science-translational-medicine
  • June 2020                               https://www.chop.edu/news/study-involving-chop-researchers-could-lead-more-precise-treatment-acute-myeloid-leukemia
  • June 2020                               https://www.ntu.ac.uk/about-us/news/news-articles/2020/06/study-paves-way-for-faster,-more-accurate-therapies-for-hard-to-treat-leukaemia-patients
  • May 2020                                https://aml-hub.com/medical-information/aacr-2020-or-patients-with-altered-tp53-rr-aml-have-increased-tumor-immune-infiltration-and-show-sensitivity-to-flotetuzumab
  • April 2020                                https://www.cancerresearch.org/blog/april-2020/aacr20-day-1-breast-cancer-lung-cancer-microbiome
  • April 2020                                http://ir.macrogenics.com/news-releases/news-release-details/macrogenics-announces-presentation-flotetuzumab-translational
  • January 2020                          https://amlglobalportal.com/medical-information/response-to-flotetuzumab-a-bispecific-cd123-cd3-molecule-is-seen-in-refractory-patients-with-acute-myeloid-leukemia-and-may-depended-on-tumor-microenvironment
  • November 2019                      https://www.mdedge.com/hematology-oncology/article/212531/aml/will-tp53-mutated-aml-respond-immunotherapy
  • November 2019                      http://blog.nanostring.com/the-era-of-spatial-transcriptomics-falls-into-place-at-sitc-2019/
  • November 2019                      https://www.aitimejournal.com/news/nanostring-highlights-the-results-of-research-presented-at-the-2019-annual-meeting-of-the-society-of-immunotherapy-for-cancer-sitc
  • September 2019                     https://www.bloomberg.com/press-releases/2019-09-30/macrogenics-presents-margetuximab-data-in-gastroesophageal-cancer-at-the-esmo-2019-congress
  • July 2019                                NTU Press Release; https://www.ntu.ac.uk/about-us/news/news-articles/2019/07/gene-signature-reveals-the-severity-of-disease-in-patients-with-blood-cancer
  • April 2019                                Vice Chancellor April Video; https://nottinghamtrentuniversity.wistia.com/medias/mry9vhyf5c?_cldee=c2VyZ2lvLnJ1dGVsbGFAbnR1LmFjLnVr&recipientid=lead-c0c7ca8a9fede811a97e00224800bb9b-d1ee2091b776426d941e19ab054b0620&esid=a7ab7f2e-a757-e911-a989-00224800cf35
  • January 2019                          BBC East Midlands Today (https://www.bbc.co.uk/iplayer/episode/b0bw49zs/east-midlands-today-lunchtime-news-02012019)
  • December 2018                      https://www.macrogenics.com/news/phase-1-expansion-cohort-oral-presentations-for-flotetuzumab-macrogenics-cd123-x-cd3-dart-molecule-in-relapsedrefractory-acute-myeloid-leukemia-presented-at-60th-ash-annual-meeting/
  • November 2018                      https://nanostring.gcs-web.com/news-releases/news-release-details/nanostring-technologies-highlights-advances-precision-oncology-2
  • November 2018                      NTU News (https://www.ntu.ac.uk/about-us/news/news-articles/2018/11/could-immune-system-spark-new-therapies-for-hard-to-treat-blood-cancer)
  • February 2018                        FHP Living: http://www.fhpliving.co.uk/news/fhp-living-visit-john-van-geest-cancer-research-centre/
  • February 2018                        Haematology News: https://www.mdedge.com/hematologynews/article/157733/aml/aml-immune-profiles-correlate-relapse-free-survival
  • January 2018                          AML Global Portal: http://www.amlglobalportal.com/medical-information/identification-of-phenotypic-profiles-in-children-and-adult-patients-with-aml-using-immune-gene-expression-profiling-aml-global-portal-coverage-at-2018-asco-sitc
  • January 2018                          East Midlands Institute of Directors; https://www.iod.com/Portals/0/PDFs/Regions/East%20Midlands/IoD%20East%20Mids%20Jan%202018.pdf?ver=2018-01-10-092204-610
  • December 2017                      Q&A with Dr Sergio Rutella: Multi-Analyte studies in acute myeloid leukaemia (http://blog.nanostring.com/qa-with-dr-sergio-rutella-multi-analyte-studies-in-acute-myeloid-leukemia/)
  • December 2017                      http://investors.nanostring.com/releasedetail.cfm?releaseid=1051128
  • December 2017                      Nottingham Trent University Donor Report 2017; http://www.ntualumni.org.uk/file/Shaping-Futures-2017.pdf

Sponsors and collaborators

Current research is being conducted with the collaboration of:

  • Martin Bornhäuser, MD, Professor of Haematology/Oncology, Co-Head of Department of Internal Medicine I, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
  • Jan K. Davidson-Moncada, MD PhD, Chief Medical Officer, Wugen, St. Louis, MO, USA
  • John F. DiPersio, MD PhD, Professor and Director, Centre for Gene and Cellular Immunotherapy (CGCI), Washington University School of Medicine, St. Louis, MO, USA
  • Sara Ghorashian, MD PhD, Consultant Paediatric Haematologist and Honorary Senior Lecturer, UCL Great Ormond Street Institute of Child Health, London, UK
  • Ivana Gojo, MD, Co-Director, Leukemia Drug Development Program, Associate Professor of Oncology, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, USA
  • Mohammad Ilyas, MD, Professor of Pathology, Faculty of Medicine & Health Sciences, University of Nottingham, UK
  • Leo Luznik, MD, Professor of Oncology, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, USA
  • Mark D. Minden, MD, Princess Margaret Cancer Centre, University Health Network (UHN), Toronto, Canada
  • Marc Schmitz, MD, Professor of Immunology and Head of NCT/UCC Immune Monitoring Unit, Institut für Immunologie, Medical Faculty Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
  • Barbara Seliger, PhD, Professor and Director, Institute for Medical Immunology, Martin Luther University, Halle-Wittenberg, Germany
  • Sarah K. Tasian, MD, Chief of the Haematologic Malignancies Program at Children’s Hospital of Philadelphia (CHOP), Division of Oncology, Children’s Hospital of Philadelphia, USA

Recent research funding:

  • Immunogenomic determinants of response to memory-like NK cells in patients with relapsed/refractory acute myeloid leukemia (AML) (2022). Wugen, St. Louis, MO, United States of America
  • Identifying immune biomarkers of disease control in multiple sclerosis using autologous haematopoietic stem cell transplantation (AHSCT) (2022-2024). Sheffield Hospital Charity, Sheffield, UK, £298,408. In collaboration with Professors Basil Sharrack and John Snowden, Sheffield Teaching Hospitals NHS Foundation Trust.
  • Establishing a bioinformatics pipeline to analyse cancer immunotherapy RNA-sequencing datasets and to develop a predictive biomarker (2022). MacroGenics Inc., Rockville, MD, United States of America
  • Investigating the cellular content of HSCT donor/graft and patient samples using immune cell profiling. Anthony Nolan Research Institute, London, £22,000 (Co-Lead: Dr Diana Hernandez).
  • 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
  • PhD Programme (2017-2021): "Implementation of a novel immune gene profiling platform for the generation and analysis of high-dimensional transcriptomic data from human tumours" (co-funded by NanoString Technologies Inc., USA).
  • Microenvironmental targets for restoring anti-tumour immunity in childhood acute leukaemia, Qatar National Research Fund (2016-2021), NPRP8-2297-3-494; $800,160
  • Alterations of A-to-I RNA editing in acute myeloid leukaemia, Italian Ministry of University and Scientific Research (PRIN; 2012-2014), PRIN-2012; #2012NA9E9Y_004, €374,413
  • 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 Economy and Occupation) (2013-2014), €410,000
  • Molecular determinants of immune dysfunction in childhood leukaemia, Bambino Gesú Children’s Hospital (2012-2013), €100,000
  • Mechanisms underpinning immune tolerance in human tumours and identification of novel strategies to restore immune surveillance, Italian Ministry of University and Scientific Research (PRIN; 2011-2013), PRIN-2009; #2009XMZPKW_002, €273,080
  • Hepatocyte growth factor and immune dysfunction in multiple myeloma, Italian Association for Cancer Research (2009-2012; IG-8556), €150,000

Publications

Rutella S, Vadakekolathu J, Mazziotta F, Reeder S, Yau TO, Mukhopadhyay R, Dickins B, Altmann H, Kramer M, Knaus H, Blazar BR, Radojcic V, Zeidner JF, Arruda A, Minden MD, Tasian SK, Bornhäuser M, Gojo I, Luznik L. Signatures of immune senescence predict outcomes and define checkpoint blockade-unresponsive microenvironments in acute myeloid leukemia. medRxiv 2022; DOI: https://www.medrxiv.org/content/10.1101/2022.02.08.22270578v1.

Corradi G, Bassani B, Simonetti G, Sangaletti S, Vadakekolathu J, Fontana M, Pazzaglia M, Gulino A, Tripodo C, Cristiano G, Bandini L, Ottaviani E, Ocadlikova D, Piccioli M, Martinelli G, Colombo MP, Rutella S, Ciciarello M, Curti A. Release of IFN-gamma by acute myeloid leukemia cells remodels the bone marrow immune microenvironment by inducing regulatory T cells. Clinical Cancer Research 2022 Mar 29; clincanres.3594.2021. DOI: 10.1158/1078-0432.CCR-21-3594.

  1. Accompanying Editorial authored by Ferrell PB & Kordasti S: “Hostile Takeover: Tregs expand in IFN-gamma-rich AML microenvironment”. Clinical Cancer Research 2022; clincanres.1030.2022. https://doi.org/10.1158/1078-0432.CCR-22-1030.

Ragaini S, Wagner S, Marconi G, Parisi S, Sartor C, Nanni J, Cristiano G, Talami A, Olivi M, Ocadlikova D, Ciciarello M, Corradi G, Ottaviani E, Papayannidis C, Paolini S, Vadakekolathu J, Cavo M, Rutella S*, Curti A*. An IDO1-related immune gene signature predicts overall survival in acute myeloid leukemia. Blood Advances 2022 Jan 11; 6(1): 87-99.*Joint senior authors.  DOI: https://doi.org/10.1182/bloodadvances.2021004878

Uy GL, Aldoss I, Foster MC, Sayre PH, Wieduwilt MJ, Advani AS, Godwin JE, Arellano ML, Sweet KL, Emadi A, Ravandi F, Erba HP, Byrne M, Michaelis LC, Topp MS, Vey N, Ciceri F, Carrabba MG, Paolini S, Huls GA, Jongen-Lavrencic M, Wermke M, Chevallier P, Gyan E, Recher C, Stiff PJ, Pettit KM, Löwenberg B, Church SE, Anderson E, Vadakekolathu J, Santaguida MT, Rettig MP, Muth J, Curtis T, Fehr E, Guo K, Zhao J, Bakkacha O, Jacobs K, Tran K, Kaminker P, Kostova M, Bonvini E, Walter RB, Davidson-Moncada JK, Rutella S, DiPersio JF. Flotetuzumab as salvage immunotherapy for refractory acute myeloid leukemia. Blood 2021; 137 (6): 751–762. DOI: 10.1182/blood.2020007732.

  1. Commentary authored by Gill S: DARTs point the way forward in AML. Blood 2021; 137 (6): 720–721
  2. Covered by a Blood Podcast (https://ashpublications.org/blood/pages/blood_podcast), 11 February 2021
  3. Covered by a Diffusion Article published on April 23, 2021 by the Hematologist  ("New Hope for Antibody-based Immunotherapy for AML: Will the DART Hit the Bullseye?") authored by Kristen M. O'Dwyer and Nancy Torres (https://ashpublications.org/thehematologist/article/475870/New-Hope-for-Antibody-based-Immunotherapy-for-AML)

Cesano A, Cannarile MA, Gnjatic S, Gomes B, Guinney J, Karanikas V, Karkada M, Kirkwood JM, Kotlan B, Masucci GV, Meeusen E, Monette A, Naing A, Thorsson V, Tschernia N, Wang E, Wells D, Wyant TL, Rutella S. The Society for Immunotherapy of Cancer biomarkers resource document: clinical biomarkers and data sharing Volume II - Practical challenges. Journal for Immunotherapy of Cancer 2020 Dec; 8 (2): e001472. DOI: 10.1136/jitc-2020-001472.

Rutella S, Cannarile MA, Gnjatic S, Gomes B, Guinney J, Karanikas V, Karkada M, Kirkwood JM, Kotlan B, Masucci GV, Meeusen E, Monette A, Naing A, Thorsson V, Tschernia N, Wang E, Wells D, Wyant TL, Cesano A. The Society for Immunotherapy of Cancer biomarkers resource document: clinical biomarkers and data sharing Volume I - Conceptual challenges. Journal for Immunotherapy of Cancer 2020 Oct; 8 (2): e001389. DOI: 10.1136/jitc-2020-001389.

*Lai C, *Vadakekolathu J (*=equal contributors), Reeder S, Church SE, Hood T, Lourdusamy A, Rettig MP, Aldoss I, Advani AS, Godwin J, Wieduwilt MJ, Arellano M, Muth J, Yau TO, Ravandi F, Sweet K, Altmann H, Foulds GA, Stölzel F, Middeke JM, Ciciarello M, Curti A, Valk PJM, Löwenberg B, Gojo I, Bornhäuser M, DiPersio JF, Davidson-Moncada JK, Rutella STP53 abnormalities correlate with immune infiltration and associate with response to flotetuzumab immunotherapy in acute myeloid leukemia. Blood Advances 2020; 4 (20): 5011-24.

Vadakekolathu J, Minden MD, Hood T, Church SE, Reeder S, Altmann H, Sullivan A, Viboch E, Patel T, Ibrahimova N, Warren SE, Arruda A, Liang Y, Smith TH, Foulds GA, Bailey MD, Gowen-MacDonald J, Muth J, Schmitz M, Cesano A, Pockley AG, Valk PJM, Löwenberg B, Bornhäuser M, Tasian SK, Rettig MP, Davidson-Moncada JL, DiPersio JF, Rutella S. Immune landscapes predict therapeutic resistance, immunotherapy response and clinical outcomes in acute myeloid leukemia. Science Translational Medicine 2020; 12 (Issue 546): eaaz0463. DOI: 10.1126/scitranslmed.aaz0463

This study was covered by a Diffusion Article published by The Hematologist ("Does the Immune System Matter in Treatment for AML?"), ASH News and Reports, and authored by Drs Jacqueline Taylor and Steven Lane. Please follow the link to the article and listen to an American Society of Hematology podcast where Dr Lane and Professor Rutella discuss the role of the immune system in the treatment of acute myeloid leukaemia (https://ashpublications.org/thehematologist/article/463586/Does-the-Immune-System-Matter-in-Treatment-for-AML).

Uy GL, Aldoss I, Foster MC, Sallman DA, Sweet KL, Rizzieri DA, Sayre PH, Advani AS, Emadi A, Wieduwilt MJ, Vey N, Ciceri F, Carrabba MG, Moyo T, Church SE, Rettig MP, Arellano ML, Godwin JE, Löwenberg B, Huls G, Ravandi F, Muth J, Tran K, Jongen-Lavrencic M, Timmeny E, Topp MS, Paolini S, Guo K, Curtis T, Zhao J, Vadakekolathu J, Wigginton JM, Bonvini E, Rutella S, Walter RB, Davidson-Moncada JK, DiPersio JF. Flotetuzumab, an investigational CD123×CD3 bispecific Dart® protein, in salvage therapy for primary refractory and early relapsed acute myeloid leukemia (AML) patients. Blood 2019; 134 (Supplement_1): 733. https://doi.org/10.1182/blood-2019-122073.

Vadakekolathu J, Minden MD, Hood T, Church SE, Reeder S, Altmann H, Sullivan AH, Viboch EJ, Patel T, Ibrahimova N, Warren SE, Arruda A, Schmitz M, Liang Y, Cesano A, Pockley AG, Valk P, Löwenberg B, Bornhäuser M, Tasian SK, Rettig MP, Davidson-Moncada JK, DiPersio JF, Rutella S. Immune landscapes predict chemotherapy resistance and anti-leukemic activity of flotetuzumab, an investigational CD123×CD3 bispecific Dart® molecule, in patients with relapsed/refractory acute myeloid leukemia. Blood 2019; 134 (Supplement_1): 460. https://doi.org/10.1182/blood-2019-121870.

Rutella S, Vadakekolathu J, Reeder S, Ashforth J, Courtney M, Coutts A, Hood T, Church S, Coveney C, Davidson-Moncada J, Meinel J, Schmitz M, Marincola FM, Bornhäuser M. Immune infiltration correlates with TP53 mutational status in a multi-cohort acute myeloid leukemia study.  Journal for Immunotherapy of Cancer 2019; 7 (Supplement_1): O3. https://doi.org/10.1186/s40425-019-0764-0

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

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 JF. Phase 1 cohort expansion of flotetuzumab, a CD123×CD3 bispecific DART® protein in patients with relapsed/refractory acute myeloid leukemia (AML). Blood 2018 132:764. 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. 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 Jun 26;23(13):3946-3959.e6. 10.1016/j.celrep.2018.05.082.

Perspective and Commentary (“Neutrophils take a different tack”) published in Science 2018; 361 (6400): 376-7. DOI: 10.1126/science.361.6400.376-f.

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. Journal of Clinical Oncology 2018; 36 (Suppl. 5S; A#50). 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. Journal for Immunotherapy of Cancer 2017 Mar 21;5:21. 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. 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. 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. Journal of Allergy and Clinical Immunology 2014 Apr;133(4):1215-8. 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. 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. 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. 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. 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. 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. Clinical Cancer Research 2009 Jul 1;15(13):4299-311. 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. European Heart Journal 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