Education
- 1973 M.D., University of Milan, Italy
- 1976 Specialist in Oncology, University of Pavia, Italy
Academic Background
- 1973-1975 Research assistant Department of Tumor Immunobiology and Chemotherapy, Istituto di Ricerche Farmacologiche 鈥淢ario听Negri鈥�, Milan, Italy.
- 1975-1976 Visiting fellow at the Department of Tumor Immunology, Chester Beatty Research Institute, Belmont, Sutton, Surrey, England.
- 1978 and 1979 Visiting fellow at the Laboratory of Immunodiagnosis, NIH, Bethesda, MD., USA, supported by a NATO Grant.
- 1979-1981 Senior investigator, Department of Tumor Immunology and Negri鈥�, Milan, Italy
- 1981-1996 Chief, Laboratory of Immunology, Istituto di Ricerche Farmacologiche 鈥淢ario Negri鈥�, Milan, Italy.
- 1987 Eleanor Roosvelt UICC Scholar, Laboratory of Molecular Immunoregulation, NIH, Frederick, MD., USA.
- 1994 to 2001 Full Professor of General Pathology, School of Medicine, University of Brescia, Italy.
- 1996 to 2005 Head, Department of Immunology and Cell Biology, Istituto di Ricerche Farmacologiche 鈥淢ario Negri鈥�, Milan, Italy.
- 2001 to 2014 Full Professor of General Pathology, School of Medicine, State University听of Milan, Italy
Main Contributions
- Tumor biology.听 Demonstration in the late 鈥�70s of the protumor function of tumor-associated macrophages 听(TAM, an acronym now generally used and coined by him in the 鈥�70s)听 linking inflammation and cancer (reviewed in Balkwill and Mantovani, Lancet, 2001). TAM as a prototypic M2-like population (Mantovani et al., Nature 2008; Balkwill et al., Cancer Cell 2005).听 First molecular linking of a genetic event (RET/PTC rearrangement)听 causing cancer in humans to the construction of an inflammatory microenvironment (Borrello et al., PNAS 2005). Proof of principle that targeting tumor promoting macrophages has therapeutic value in humans (Germano et al, Cancer Cell 2013). Demonstration that PTX3 is an extrinsic oncosuppressor regulating Complement and macrophage driven tumor promoting inflammation (Bonavita et al Cell 2015). Alberto Mantovani is recognized among his peers as a forerunner in the 鈥�70s and a 鈥渇ounding father鈥� of the renaissance of the inflammation-cancer connection.
- Chemokines.听Original description and role in TAM recruitment of a unique monocyte attractant, Monocyte Chemotactic听 Protein-1 (CCL2), as tumor-derived chemotactic factor (Bottazzi et al, Science 1983). Characterization of chemokines and role in pathophysiology, including dendritic cell and polarized T cell migration. Induction of chemokine production by IL-6 in endothelial cells via trans-signaling, a key component of chronic inflammation and cancer (Romano et al, Immunity 1997). Characterization of D6 as a decoy receptor for inflammatory CC chemokines (Mantovani et al, Nature Rev. Immunol 2006). Role of chemokines in carcinogenesis (for a recent contribution Bonavita et al Cell 2015).听 Role of the chemokines vMIPs in attracting Th2 cells and role of D6 (ACKR2) in Kaposi鈥檚 sarcoma.
- IL-1/Toll-like receptors (TLR).听Endothelial cell activation by IL-1 and cytokines (Rossi et al., Science 1985; Bussolino et al, Nature 1989; Romano et al, Immunity 1997). Identification of the type II receptor as a decoy receptor, a novel concept in biology (Colotta et al, Science 1993); the discovery of a decoy receptor represented a paradigm shift after the original definition of the concept of 鈥渞eceptor鈥� by Langley at the 1930鈥�; decoy receptors are now recognized as a general,听 evolutionary conserved strategy to tune cytokines, chemokines and growth factors. Cloning of an intracellular isoform of the IL-1 receptor antagonist (Muzio et al., J. Exp. Med.听 1995). First demonstration of MyD88 as the adaptor of mammalian Toll-Like Receptors (TLR) and identification of downstream transducers (Muzio et al., J. Exp. Med. 1998). Cloning and characterization of TIR8/SIGIRR (IL-1R8), a negative regulator of IL-1 receptor and TLR signalling (Garlanda, et al, Immunity 2013). Role in carcinogenesis.
- Humoral innate immunity: cloning (cDNA and genomic, mouse and human), structural and functional characterization of the first long pentraxin PTX3 as an IL-1 inducible gene (Garlanda et al, Nature 2002; Jeannin et al, Immunity 2005; Jaillon et al. J. Exp Med 2007听; Deban et al, Nature Immunol. 2010; Jaillon et al. Immunity 2014; Bonavita et al. Cell 2015); structural immunobiology; role as a paradigm for humoral innate immunity; role as an extrinsic oncosuppresor in murine and human tumors regulating Complement and macrophage driven tumor promoting inflammation (Bonavita et al. Cell 2015); diagnostic and therapeutic translation (Cunha et al New England J. Med. 2014; ongoing). Thus, a regulator of macrophage-driven tumor promoting inflammation is a bona fide cancer gene, silenced in selected human tumors such as colorectal cancer, a finding now independently confirmed.
Originals
- Bonavita E, Gentile S, Rubino M, Maina V, Papait R, Kunderfranco P, Greco C, Feruglio F, Molgora M, Laface I, Tartari S, Doni A, Pasqualini F, Barbati E, Basso G, Galdiero MR, Nebuloni M, Roncalli M, Colombo PG, Laghi L, Lambris JD, Jaillon S, Garlanda C,听Mantovani A. 鈥�听PTX3 is an extrinsic oncosuppressor regulating complement-dependent inflammation in cancer.听Cell 160: 700-714, 2015.
Reviews
- Mantovani A., Marchesi F., Laghi L., Malesci A., Allavena P. 听鈥撎�Tumor-associated macrophages as treatment targets in oncology.听Nature Rev, Clin. Oncol.;听 adv. online publication 2017 doi: 10.1038/nrclinonc.2016.217
- Sica A,听Mantovani A.听鈥撎�Macrophage plasticity and polarization: in vivo veritas.听J Clin Invest. 122: 787-795, 2012.
- Mantovani A, Allavena P, Sica A, Balkwill F 鈥撎�Cancer-Related Inflammation.听Nature 454: 436-444, 2008.
- Mantovani, A., Romero, P., Paluka, AK., Marincola, FM. 鈥撎�Tumor immunity: effector response to tumor and the influence of the microenvironment.听Lancet 371:771-783, 2008.