Alberto Mantovani: “The two aspects of my research life I like most are discussing data, and formulating hypotheses and models."

Five minutes with Alberto Mantovani, who will be awarded the 2024 Sir Hans Krebs medal from FEBS at the 48th FEBS Congress in Milano this year.
Alberto Mantovani: “The two aspects of my research life I like most are discussing data, and formulating hypotheses and models."
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Alberto Mantovani, MD, is Emeritus Professor of Pathology at the Humanitas University in Milan, Scientific Director of the Istituto Clinico Humanitas, and Chair of Inflammation and Therapeutic Innovation, William Harvey Research Institute, Queen Mary University, London, UK. His attention has been focused on molecular mechanisms of innate immunity and inflammation and on the role in the tumor microenvironment and cancer progression of tumor-associated macrophages (TAMs). He has contributed to the advancement of knowledge in the field of immunology formulating new paradigms and identifying new molecules and functions. More recently he focused on COVID-19, contributing to the identification of genetic associations and of a novel severity biomarker. For his research activity he has received several national and international awards, such as the Triennial OECI Award from the Organization of the European Cancer Institutes, the Robert Koch Award for his contribution to tumor immunology and immunotherapy, the American-Italian Cancer Foundation (AICF) Prize for Excellence in Medicine, the American Association for Cancer Research International Pezcoller Award for Extraordinary Achievement in Cancer Research and, most recently, the CIMT Lifetime Achievement Award. The broad impact of his contributions is testified by citations: as of November 2023, he has over 166,000 citations and an H-index of 183 (Scopus).

Tell us about one of your favourite published papers from your lab

In the late 1970s I had found that tumor-associated macrophages promoted growth of metastatic tumors. On this basis I hypothesized that tumor cells should produce macrophage chemoattractants. We found that tumor cells produced a chemoattractant active on monocytes and not on neutrophils, a unique property at that time. The Science paper below on this finding was one of the first descriptions of a chemokine subsequently identified as monocyte chemotactic protein-1 (MCP-1; CCL2). We were later involved in the discovery and characterization of chemokines and their receptors. These studies contributed to a change in vision of neoplasia from a cancer cell centric view to one that encompasses the tumor microenvironment.

Bottazzi, B. et al. (1983) Regulation of the macrophage content of neoplasms by chemoattractants. Science 220, 210–212. https://doi.org/10.1126/science.6828888
Balkwill, F. and Mantovani, A. (2001) Inflammation and cancer: back to Virchow? Lancet 357, 539–545. https://doi.org/10.1016/S0140-6736(00)04046-0
Mantovani, A. et al. (2008) Cancer-related inflammation. Nature 454, 436–444. https://doi.org/10.1038/nature07205

What’s currently your favourite molecule?

I will choose here PTX3, the first member of the long pentraxin family and whose role has served as a paradigm of the humoral arm of innate immunity. We molecularly cloned PTX3 and our efforts have spanned the whole spectrum from gene identification, to structure, to function, to genetics, to translation as a novel diagnostic tool.

Garlanda, C. et al. (2002) Non-redundant role of the long pentraxin PTX3 in anti-fungal innate immune response. Nature 420, 182–186. https://doi.org/10.1038/nature01195
Mantovani, A. and Garlanda, C. (2023) Humoral innate immunity and acute-phase proteins. New Engl. J. Med. 388, 439–452. https://doi.org/10.1056/NEJMra2206346

How do you explain your work to a non-scientist?

I have been involved in science communication at various levels, from giving talks to high-school students to participation in prime time national television programs. I have written books for the general public. I feel it is our duty to communicate science, in the most simple, understandable and humble form (Karl Popper). For instance, I say that in cancer and other diseases macrophages behave as corrupted policemen, to explain our contribution to tumor immunology.

Three selected books (in Italian):
Mantovani, A. (2016) Immunità e Vaccini, Mondadori (awarded the Premio Letterario Merck per la Saggistica)
Mantovani, A. (2018) Bersaglio Mobile, Mondadori
Mantovani, A. (2021) Il Fuoco Interiore. Immunità e malattie, 2nd edn, Mondadori (awarded the literary prize Angelo Zanibelli).

What aspects of your life as a researcher do you most enjoy?

The two aspects of my research life I like most are discussing data, and formulating hypotheses and models. After a day or days of administration, boards, and review committees, discussing data is a breath of fresh air. Formulating hypotheses and models is a process that can occur at home, on a beach, or in a mountain hut.

What roles in the scientific community beyond your own research group do you see as most important?

I have played roles in scientific Societies, including serving as President of the International Union of Immunological Societies. However, work with the Global Alliance for Vaccines and Immunization (GAVI) has been a unique experience, and change of perspective towards that of the most deprived children living in low-income countries. I am now supporting the non-governmental organization (NGO) “Medici con l’Africa CUAMM”, focused on the most fragile African countries.

Clemens, J. et al. (2010) Ten years of the global alliance for vaccines and immunization: challenges and progress. Nat. Immunol. 11, 1069–1072. https://doi.org/10.1038/ni1210-1069
Medici con L’Africa CUAMM (2023) Africa, andata e ritorno, Laterza


Introduction to Alberto Mantovani’s work

Research summary

The work of the Mantovani lab is focused on the molecular mechanisms of innate immunity and inflammation, with past and current research areas of his group spanning tumor-associated macrophages, chemokines, IL-1 and Toll-like receptors, and humoral innate immunity.

Lab webpage (url): https://www.humanitas-research.com/groups/alberto-mantovani-group/

Two recent/key papers: 

Mantovani, A. and Garlanda, C. (2023) Humoral innate immunity and acute-phase proteins. New Engl. J. Med. 388, 439–452. https://doi.org/10.1056/NEJMra2206346

Ponzetta, A. et al. (2019) Neutrophils driving unconventional T cells mediate resistance against murine sarcomas and selected human tumors. Cell 178, 346–360. https://doi.org/10.1016/j.cell.2019.05.047


More information on the FEBS Sir Hans Krebs medal and plenary lecture at the 48th FEBS Congress

The Sir Hans Krebs medal is awarded annually by FEBS for outstanding achievements in Biochemistry and Molecular Biology or related sciences: www.febs.org/other-activities/prizes/febs-medals/

Alberto Mantovani will be presented with the medal at the 48th FEBS Congress on Sunday 30th June 2024 where he will deliver the FEBS Sir Hans Krebs Lecture on ‘Innate immunity and inflammation: from molecules to cancer and COVID-19’: https://2024.febscongress.org/


Top image of post: Breast tumor microenvironment, National Cancer Institute \ Carbone Cancer Center at the Univ. of Wisconsin. Tumor cells, cyan; macrophages, red; collagen fibers, green. Creator and other details at https://visualsonline.cancer.gov/details.cfm?imageid=10573

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