Alberto Mantovani

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Alberto Mantovani
Alberto Mantovani medico.jpg
Born (1948-10-29) October 29, 1948 (age 75)
Milan, Italy
Alma materUniversity of Milan
Known for
Awards Robert Koch Prize, see text for others
Scientific career
Fields Immunology
Institutions University of Milan
Humanitas University
University of Brescia
Mario Negri Institute for Pharmacological Research
Website Page at Humanitas

Alberto Mantovani Commendatore OMRI (born 29 October 1948) is an Italian physician and immunologist. He is Scientific Director of Istituto Clinico Humanitas (Humanitas Clinical and Research Center), President and Founder of the Fondazione Humanitas per la Ricerca, and Professor of Pathology at the State University of Milan. [1] He is known for his works in the roles of the immune system in the development of cancer. His research on tumor-associated macrophages (TAM, an acronym he coined) established inflammation as one of the causes of cancer. He was the first to identify monocyte chemotactic protein - 1 / CCL2 in 1983, and PTX3 in 1997. His works revealed the existence of decoy receptors in cell-signalling. He has been the most cited scientist in Italy, and one of the ten most cited immunologists worldwide. [2]

Contents

Biography

Mantovani was born in Milan [1] on 29 October 1948. [3] He studied medicine at the University of Milan and graduated ( summa cum laude ) in 1973. In 1976 he earned a specialization in oncology at the University of Pavia. Between 1973 and 1976, he worked as a visiting fellow at the Department of Tumor Immunology of the Chester Beatty Research Institute (now the Institute of Cancer Research) in Belmont, Sutton, England, where he continued the studies of Iwan Robert Evans and Peter Alexander. Between 1978 and 1979 he was a visiting fellow at the Laboratory of Immunodiagnosis at the National Institutes of Health in Bethesda, Maryland. In 1979 he was appointed Senior investigator in the Department of Tumor Immunology and Chemotherapy at the Istituto di Ricerche Farmacologiche "Mario Negri" in Milan. He became the Chief of Laboratory of the institute in 1981. In 1987 he worked at the Laboratory of Molecular Immunoregulation of NIH in Frederick, Maryland, as an Eleanor Roosvelt UICC Scholar. In 1994 he was promoted to Full Professor of General Pathology in the School of Medicine at the University of Brescia. He became Head of the Department of Immunology and Cell Biology at Istituto di Ricerche Farmacologiche "Mario Negri" in 1996. Between 2001 and 2014, he also served as Full Professor of General Pathology in the School of Medicine of the State University of Milan. Then he continued as Full Professor of General Pathology at Humanitas University in 2014. In 2005 he became the Scientific Director of Istituto Clinico Humanitas and President of Fondazione Humanitas per la Ricerca (under Humanitas University). [1] [2]

Research activities

Following the deepening of the studies by Robert Evans and Peter Alexander on the role of macrophages in tumour formation, [4] Mantovani discovered that macrophages, rather than helping to shrink the tumor, help it to grow and progress. [5] He gave the acronym for such tumor-associated macrophages as TAM. His work in 2013 showed that targeting TAM is useful for cancer treatment. [6] In 1983, his research team has discovered a protein, known as monocyte chemotactic protein - 1 / CCL2, which is part of the large superfamily of chemokines, which belong to the family of cytokines. His works help to establish the concept of "decoy receptors". From the study of the regulation of the cytokines, Mantovani was able to identify the operating principle of the decoy receptor for interleukin - 1. In 1993, his team showed interleukin-1 type II receptor acts as a decoy in the activity of interleukin 1. [7] His team identified the first member of the long pentraxins, named PTX3 in 1997. The discovery was published in a series of papers. [8] [9] [10] His team demonstrated in 2005 that the chemokine receptor D6 acts as a decoy and scavenger receptor for inflammatory chemokines. [11] In 2015 his research, published in the journal Cell , [12] showed that PTX3 gene is capable of curbing cancer by controlling inflammation.

Works

Scientific Publications

Awards

Honors

Commendatore OMRI.jpg

Mantovani was appointed "Commander" of the Order of Merit of the Italian Republic in 2005. [17] He was Fellow of the Italian Association Against Leukemias in 1973, and Fellow of the Anna Villa Rusconi Foundation in 1974. [2] He was vice-president/president the International Union of Immunological Societies from 2013 to 2016. He served on the board of the Global Alliance for Vaccines and Immunization (GAVI) between 2007 and 2010. He was president of the International Cytokine Society during 2009–2010. [18]

Related Research Articles

<span class="mw-page-title-main">Inflammation</span> Physical effects resulting from activation of the immune system

Inflammation is part of the biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. The five cardinal signs are heat, pain, redness, swelling, and loss of function.

<span class="mw-page-title-main">Cytokine</span> Broad and loose category of small proteins important in cell signaling

Cytokines are a broad and loose category of small proteins important in cell signaling. Due to their size, cytokines cannot cross the lipid bilayer of cells to enter the cytoplasm and therefore typically exert their functions by interacting with specific cytokine receptors on the target cell surface. Cytokines have been shown to be involved in autocrine, paracrine and endocrine signaling as immunomodulating agents.

<span class="mw-page-title-main">Macrophage</span> Type of white blood cell

Macrophages are a type of white blood cell of the innate immune system that engulf and digest pathogens, such as cancer cells, microbes, cellular debris, and foreign substances, which do not have proteins that are specific to healthy body cells on their surface. This process is called phagocytosis, which acts to defend the host against infection and injury.

<span class="mw-page-title-main">Interleukin 4</span> Mammalian protein found in Mus musculus

The interleukin 4 is a cytokine that induces differentiation of naive helper T cells (Th0 cells) to Th2 cells. Upon activation by IL-4, Th2 cells subsequently produce additional IL-4 in a positive feedback loop. IL-4 is produced primarily by mast cells, Th2 cells, eosinophils and basophils. It is closely related and has functions similar to IL-13.

<span class="mw-page-title-main">Interleukin 8</span> Mammalian protein found in humans

Interleukin 8 is a chemokine produced by macrophages and other cell types such as epithelial cells, airway smooth muscle cells and endothelial cells. Endothelial cells store IL-8 in their storage vesicles, the Weibel–Palade bodies. In humans, the interleukin-8 protein is encoded by the CXCL8 gene. IL-8 is initially produced as a precursor peptide of 99 amino acids which then undergoes cleavage to create several active IL-8 isoforms. In culture, a 72 amino acid peptide is the major form secreted by macrophages.

<span class="mw-page-title-main">Interleukin 32</span> Protein-coding gene in the species Homo sapiens

Interleukin 32 (IL32) is proinflammatory cytokine that in humans is encoded by the IL32 gene. Interleukin 32 can be found in higher mammals but not in rodents. It is mainly expressed intracellularly and the protein has nine different isoforms, because the pre-mRNA can be alternatively spliced. The most active and studied isoform is IL-32γ. It was first reported in 2005, although the IL-32 gene was first described in 1992. It does not belong to any cytokine family because there is almost no homology with other cytokines.

<span class="mw-page-title-main">Interleukin 30</span> Protein-coding gene in the species Homo sapiens

Interleukin 30 (IL-30) forms one chain of the heterodimeric cytokine called interleukin 27 (IL-27), thus it is also called IL27-p28. IL-27 is composed of α chain p28 and β chain Epstain-Barr induce gene-3 (EBI3). The p28 subunit, or IL-30, has an important role as a part of IL-27, but it can be secreted as a separate monomer and has its own functions in the absence of EBI3. The discovery of IL-30 as individual cytokine is relatively new and thus its role in the modulation of the immune response is not fully understood.

Chemokine ligands 4 previously known as macrophage inflammatory protein (MIP-1β), is a protein which in humans is encoded by the CCL4 gene. CCL4 belongs to a cluster of genes located on 17q11-q21 of the chromosomal region. Identification and localization of the gene on the chromosome 17 was in 1990 although the discovery of MIP-1 was initiated in 1988 with the purification of a protein doublet corresponding to inflammatory activity from supernatant of endotoxin-stimulated murine macrophages. At that time, it was also named as "macrophage inflammatory protein-1" (MIP-1) due to its inflammatory properties.

<span class="mw-page-title-main">CCL7</span> Mammalian protein found in Homo sapiens

Chemokine ligand 7 (CCL7) is a small cytokine that was previously called monocyte-chemotactic protein 3 (MCP3). CCL7 is a small protein that belongs to the CC chemokine family and is most closely related to CCL2.

<span class="mw-page-title-main">CCL17</span> Mammalian protein found in Homo sapiens

CCL17 is a powerful chemokine produced in the thymus and by antigen-presenting cells like dendritic cells, macrophages, and monocytes. CCL17 plays a complex role in cancer. It attracts T-regulatory cells allowing for some cancers to evade an immune response. However, in other cancers, such as melanoma, an increase in CCL17 is linked to an improved outcome. CCL17 has also been linked to autoimmune and allergic diseases.

<span class="mw-page-title-main">CXCL9</span> Mammalian protein found in Homo sapiens

Chemokine ligand 9 (CXCL9) is a small cytokine belonging to the CXC chemokine family that is also known as monokine induced by gamma interferon (MIG). The CXCL9 is one of the chemokine which plays role to induce chemotaxis, promote differentiation and multiplication of leukocytes, and cause tissue extravasation.

<span class="mw-page-title-main">CXCL1</span> Mammalian protein found in Homo sapiens

The chemokine ligand 1 (CXCL1) is a small peptide belonging to the CXC chemokine family that acts as a chemoattractant for several immune cells, especially neutrophils or other non-hematopoietic cells to the site of injury or infection and plays an important role in regulation of immune and inflammatory responses. It was previously called GRO1 oncogene, GROα, neutrophil-activating protein 3 (NAP-3) and melanoma growth stimulating activity, alpha (MGSA-α). CXCL1 was first cloned from a cDNA library of genes induced by platelet-derived growth factor (PDGF) stimulation of BALB/c-3T3 murine embryonic fibroblasts and named "KC" for its location in the nitrocellulose colony hybridization assay. This designation is sometimes erroneously believed to be an acronym and defined as "keratinocytes-derived chemokine". Rat CXCL1 was first reported when NRK-52E cells were stimulated with interleukin-1β (IL-1β) and lipopolysaccharide (LPS) to generate a cytokine that was chemotactic for rat neutrophils, cytokine-induced neutrophil chemoattractant (CINC). In humans, this protein is encoded by the gene CXCL1 and is located on human chromosome 4 among genes for other CXC chemokines.

<span class="mw-page-title-main">CCR2</span> Mammalian protein found in humans

C-C chemokine receptor type 2 (CCR2 or CD192 is a protein that in humans is encoded by the CCR2 gene. CCR2 is a CC chemokine receptor.

<span class="mw-page-title-main">Interleukin 1 receptor, type II</span> Protein-coding gene in the species Homo sapiens

Interleukin 1 receptor, type II (IL-1R2) also known as CD121b is an interleukin receptor. IL1R2 also denotes its human gene.

<span class="mw-page-title-main">PTX3</span>

Pentraxin-related protein PTX3 also known as TNF-inducible gene 14 protein (TSG-14) is a protein that in humans is encoded by the PTX3 gene.

<span class="mw-page-title-main">CCR9</span> Protein-coding gene in the species Homo sapiens

C-C chemokine receptor type 9 is a protein that in humans is encoded by the CCR9 gene. This gene is mapped to the chemokine receptor gene cluster region. Two alternatively spliced transcript variants have been described.

Interleukin-28 receptor is a type II cytokine receptor found largely in epithelial cells. It binds type 3 interferons, interleukin-28 A, Interleukin-28B, interleukin 29 and interferon lambda 4. It consists of an α chain and shares a common β subunit with the interleukin-10 receptor. Binding to the interleukin-28 receptor, which is restricted to select cell types, is important for fighting infection. Binding of the type 3 interferons to the receptor results in activation of the JAK/STAT signaling pathway.

Myeloid-derived suppressor cells (MDSC) are a heterogeneous group of immune cells from the myeloid lineage.

Immunology is the study of the immune system during health and disease. Below is a list of immunology-related articles.

<span class="mw-page-title-main">Decoy receptors</span>

A decoy receptor is a receptor that is able to recognize and bind specific growth factors or cytokines efficiently, but is not structurally able to signal or activate the intended receptor complex. It acts as an inhibitor, binding a ligand and keeping it from binding to its regular receptor. Decoy receptors participate in a common methods of signal inhibition and are also abundant in malignant tissues, making up a significant topic in cancer research.

References

  1. 1 2 3 "Biography—Alberto Mantovani, MD". Cancer and Metastasis Reviews. 29 (2): 239. 2010. doi: 10.1007/s10555-010-9219-2 .
  2. 1 2 3 "Mantovani Alberto, MD". www.humanitas-research.org. Humanitas Clinical and Research Center, Italy. Archived from the original on 25 June 2016. Retrieved 27 July 2016.
  3. "Curriculum vitae: Mantovani Alberto". www.forumecm.it. Retrieved 29 July 2016.
  4. Evans, R.; Alexander, P. (1972). "Mechanism of Immunologically Specific Killing of Tumour Cells by Macrophages". Nature. 236 (5343): 168–170. Bibcode:1972Natur.236..168E. doi:10.1038/236168a0. PMID   4553694. S2CID   4256131.
  5. Bonavita, E; Galdiero, MR; Jaillon, S; Mantovani, A (2015). Phagocytes as Corrupted Policemen in Cancer-Related Inflammation. Vol. 128. pp. 141–71. doi:10.1016/bs.acr.2015.04.013. ISBN   9780128023167. PMID   26216632.{{cite book}}: |journal= ignored (help)
  6. "The Milstein Award: Alberto Montavani". International Cytokine and Interferon Society (ICIS). Archived from the original on 7 August 2016. Retrieved 29 July 2016.
  7. Colotta, F; Re, F; Muzio, M; Bertini, R; Polentarutti, N; Sironi, M; Giri, J.; Dower, S.; Sims, J.; Mantovani, A (1993). "Interleukin-1 type II receptor: a decoy target for IL-1 that is regulated by IL-4". Science. 261 (5120): 472–475. Bibcode:1993Sci...261..472C. doi:10.1126/science.8332913. PMID   8332913.
  8. Vouret-Craviari, V; Matteucci, C; Peri, G; Poli, G; Introna, M; Mantovani, A (1997). "Expression of a long pentraxin, PTX3, by monocytes exposed to the mycobacterial cell wall component lipoarabinomannan". Infection and Immunity. 65 (4): 1345–1350. doi:10.1128/IAI.65.4.1345-1350.1997. PMC   175138 . PMID   9119472.
  9. Basile, A; Sica, A; d'Aniello, E; Breviario, F; Garrido, G; Castellano, M; Mantovani, A; Introna, M (1997). "Characterization of the promoter for the human long pentraxin PTX3. Role of NF-kappaB in tumor necrosis factor-alpha and interleukin-1beta regulation". The Journal of Biological Chemistry. 272 (13): 8172–8178. doi: 10.1074/jbc.272.13.8172 . PMID   9079634.
  10. Bottazzi, B; Vouret-Craviari, V; Bastone, A; De Gioia, L; Matteucci, C; Peri, G; Spreafico, F; Pausa, M; D'Ettorre, C; Gianazza, E; Tagliabue, A; Salmona, M; Tedesco, F; Introna, M; Mantovani, A (1997). "Multimer formation and ligand recognition by the long pentraxin PTX3. Similarities and differences with the short pentraxins C-reactive protein and serum amyloid P component". The Journal of Biological Chemistry. 272 (52): 32817–32823. doi: 10.1074/jbc.272.52.32817 . PMID   9407058.
  11. de la Torre, Yeny Martinez; Locati, Massimo; Buracchi, Chiara; Dupor, Jana; Cook, Donald N.; Bonecchi, Raffaella; Nebuloni, Manuela; Rukavina, Daniel; Vago, Luca; Vecchi, Annunciata; Lira, Sergio A.; Mantovani, Alberto (2005). "Increased inflammation in mice deficient for the chemokine decoy receptor D6". European Journal of Immunology. 35 (5): 1342–1346. doi: 10.1002/eji.200526114 . PMID   15789340. S2CID   39418935.
  12. Bonavita, Eduardo; Gentile, Stefania; Rubino, Marcello; Maina, Virginia; Papait, Roberto; Kunderfranco, Paolo; Greco, Carolina; Feruglio, Francesca; Molgora, Martina; Laface, Ilaria; Tartari, Silvia; Doni, Andrea; Pasqualini, Fabio; Barbati, Elisa; Basso, Gianluca; Galdiero, Maria Rosaria; Nebuloni, Manuela; Roncalli, Massimo; Colombo, Piergiuseppe; Laghi, Luigi; Lambris, John D.; Jaillon, Sébastien; Garlanda, Cecilia; Mantovani, Alberto (2015). "PTX3 Is an Extrinsic Oncosuppressor Regulating Complement-Dependent Inflammation in Cancer". Cell. 160 (4): 700–714. doi: 10.1016/j.cell.2015.01.004 . PMID   25679762.
  13. "Biotecnologie: Ricerca e Futuro a Biotec Award 1998". 22 June 1998.
  14. 1 2 "Biography—Alberto Mantovani, MD". Cancer and Metastasis Reviews. 29 (2): 239. 2010. doi: 10.1007/s10555-010-9219-2 .
  15. "Featuring the Guest Editor Alberto Mantovani". 4 December 2020.
  16. "THE PEZCOLLER FOUNDATION-AACR INTERNATIONAL AWARD". Pezcoller Foundation. Retrieved 6 November 2019.
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