The BSI was saddened to learn about the recent death of our Member, Professor Vincenzo Cerundolo FRS. Enzo has been part of the BSI for three decades, greatly contributing to the field as an active member since 1990, being involved with the BSI Oxford Immunology Group and speaking at numerous events.
Enzo was born in Italy, in Lecce, in the region known as the heel of the country. As many others, after completing the Liceo Scientifico De Giorgi in Lecce, he moved to northern Italy, to study medicine in Padova, where he also did his PhD in immunology and clinical training in medical oncology, under the supervision of Dino Collavo and Paola Zanovello. He then moved to the UK in 1988 with an EMBO fellowship to work with Professor Alain Townsend. His wife Lucia, and their daughter Giulia, followed in 1989.
With Alain, Enzo made seminal discoveries in the field of peptide antigen presentation and defined the role of TAP transporters. His training in oncology influenced his interest in tumour immunology and when he transitioned to independence, he applied his knowledge to the understanding of how tumour antigens are presented and the role of crosspresentation in anti-tumour responses. Having characterised TAP-dependent antigen presentation with Alain, with his first postdoctoral fellows and PhD students he then described families of patients with TAP deficiency and peculiar necrotising granulomatous skin lesions. This clinical syndrome also sparked his interest in unconventional T cell biology, where after successfully refolding CD1d molecules and generating lipid antigen loaded tetramers, his lab made several contributions towards the characterisation of molecular mechanisms of lipid antigen presentation.
They then identified iNKT cell agonists with different stimulatory capacity, and with Prof Yvonne Jones determined the crystal structure of the dominant iNKT cell antigen, α-GalCer, bound to human CD1d. Serendipitously, the crystal contained units of unloaded CD1d molecules and Enzo put forward an interesting hypothesis for the existence of chaperone lipids assisting in the folding of CD1 molecules, later verified experimentally. He was so thrilled to see the crystal images, on his return from the CD1 symposium in September 2004, in Heron Island, Australia.
Enzo’s lab rapidly grew in the WIMM (Weatherall Institute of Molecular Medicine), from a few members in the top corner of the institute, to larger labs strategically positioned between CRUK facilities (he was funded by CRUK for over 20 years, moving from small projects to ambitious programme grants) and the MRC Human Immunology Unit. In addition, he had satellite labs in the main John Radcliffe Hospital in Oxford, including a GMP (Good Manufacturing Practices) suite for immune-monitoring of clinical trials. All these activities, and more, came together when he was appointed Director of the MRC Oxford University Human Immunology Unit in 2010, a position he held until his death.
He showed that tolerance can be induced in adults, studied graft versus host disease, and explored the immunoregulatory role of T lymphocytes. The concept that we can ‘tolerise’ using powerful immunosuppressive tools was an indirect product of his work
Enzo’s family also grew, with the birth of his son Marco, in 2001. Enzo was very close to both his family in Oxford and his roots in Puglia, where he spent the summer holidays most years, together with visits to the Dolomites with his close friends from Padova, Fabio and Marina. He always returned tanned and recharged, full of ideas for new experiments and collaborations.
Enzo’s infectious enthusiasm for science and his intellectual breadth drove interesting collaborations, which led him to explore a variety of immunological questions, including autoimmunity in Addison’s patients. Whenever possible, Enzo was keen to link basic research findings with clinical observations, to ultimately improve patients’ therapies. Indeed, he contributed as a founding member to the set-up of iOX Therapeutics, a spin off company stemming from his studies on α-GalCer analogues, with the aim of using different formulations of iNKT cell agonists to enhance antigenspecific immune responses in cancer patients. He characterised the famous NY-ESO-1 specific, HLA-A2 restricted TCR, 1G4, which has now been genetically engineered elsewhere and is used in adoptive T cell therapy. As a consequence of his broad interests, he designed studies on the tumour microenvironment, in an attempt to understand why tumour cells manage to survive a metabolic altered milieu, but this impairs T cell recognition.
Enzo’s enthusiasm for research was transferred to the many students, postdocs and research assistants he mentored over his long career. Whenever possible, he tried to have weekly meetings with each of his junior members to discuss the direction of travel. He had great intuition and always suggested the right avenue forward. Once director of the Human Immunology Unit (HIU), he had an excellent understanding of the strengths of human immunology and through facilitating collaborations promoted a dynamic, stimulating work environment, which attracted basic scientists as well as several clinician scientists. He continued the tradition of annual meetings to share scientific results within the Unit groups and took great pride in showcasing the Unit’s achievements to the Advisory board. HIU days were always a success, leading to new collaborations, new ideas. Under his leadership the Unit went from strength to strength.
Enzo’s smile, sense of humour and extensive knowledge facilitated his interactions with several members of the WIMM, not least Sir Peter Radcliffe, who at the time of Enzo’s transition to independence, was performing the experiments for which he was awarded the Nobel Prize last year. They even shared a lab at some point. Enzo also collaborated with the wider Oxford immunology community, and several UK labs. He was internationally recognised in the cancer immunology field, through his affiliation with the Ludwig Institute, in the antigen presentation field and in the CD1 field. As a testimony for his many scientific contributions, he received several recognitions, including Fellowships of the Academy of Medical Sciences, the Royal College of Pathology, and of the Israel Academy of Medical Sciences. In 2018 he was elected a Fellow of the Royal Society. He was also a Fellow of Merton College in Oxford. He co-organised a Keystone Meeting on myeloid cells and two international CD1/MR1 conferences.
In one of the saddest ironies of life, Enzo was diagnosed in 2017 with lung cancer and without any doubts he applied his scientific rigour to his treatment. A grim tumour for a non-smoker, as it does not carry as many mutations to awaken the immune system, Enzo was nevertheless willing to try every experimental treatment available, to harness the immune system he had studied in so much detail. With the guidance of international colleagues expert in the field, he went through rounds of chemotherapy, checkpoint inhibitors, vaccines and radiotherapy.
Throughout this battle, his strength and his positive energy were remarkable, “business as usual”, he would say. Lab meetings were held over Skype and long emails were used when he needed to stay away from crowds at the nadir of his haematological values. Enzo was always scientifically present, even more, as he delegated some of the administrative work. Every success was an occasion to celebrate – papers, graduations of DPhil students, the well-deserved election as Fellow of the Royal Society in the Spring of 2018 and recently, the CD1/MR1 symposium, held in Oxford in September 2019.
His sudden departure at the beginning of the year, a few weeks after his 60th birthday, took us all by surprise. We fondly remember the last HIU day in mid-December 2019 and the plans for the next grants and the next MRC quinquennial review. Enzo leaves a gaping hole in all our lives and his friendly, encouraging smile is sorely missed, but we are carrying on his scientific legacy, as he would have liked us to do.
Clinical Research Fellow
MRC Human Immunology Unit
University of Oxford