Team Andrea Ponzetta: Unconventional T cells in human pathology

The team is exploring the heterogeneity and the functional potential of unconventional T cells in human pathology. Our research interest is focused on a subset of immune cells that are at the crossroad between innate and adaptive immunity: unconventional T cells (UTC).

The Andrea Ponzetta team is part of Niklas Björkström group at the Center of Infectious Medicine.

Our research interest is focused on a subset of immune cells that are at the crossroad between innate and adaptive immunity: unconventional T cells (UTC). While some members of this family (e.g. iNKT and MAIT cells) have been characterized in detail in terms of antigen recognition and developmental trajectory, fundamental biological aspects of other components of the UTC group remain currently elusive.

Our research questions stem from our recent findings showing that a novel population of UTC (DNTβ cells) displayed a prominent antitumor activity in preclinical models (Ponzetta et al, Cell 2019). However, whether similar phenomena occur in humans is currently unclear. Thus, in our team we study human DNTβ by tackling several aspects of their biology, in homeostasis and pathological conditions.

In parallel to the mapping of DNTβ localization, ontogeny and maturation process in humans, we aim at understanding the role and possible translational value of innate-like T cells in both hematological malignancies and in solid tumors. In addition, we have started to investigate how DNTβ participate to the anti-viral immune response, for instance against SARS-CoV-2 infection.

Team leader

    Andrea Ponzetta

    Team Leader

    In 2014 Andrea completed his PhD in Immunology at Sapienza University of Rome, where he focused on NK cell trafficking and development. He then moved as a postdoctoral fellow to Humanitas Clinical and Research Center in Milan to study the role of neutrophils in carcinogenesis in solid tumors and their interaction with unconventional T cells. At CIM since 2020, he is currently interested in the biology of innate-like lymphocytes and in their impact in human tumors. When not at work, Andrea enjoys travelling, cooking and hiking.

    Open positions

    We always want to get in touch with talented potential co-workers with questions on innate-like T cells and tumor immunology. If you are interested in doing research within our team as a student or as a postdoc, please contact the Team Leader at: andrea.ponzetta@ki.se

    Collaborations

    Our research at the Center of Infectious Medicine benefits from the collaboration with several research units within and outside KI, and is closely connected with our clinical collaborators at the Karolinska University Hospital. In our team we use a range of single cell technologies, including high-dimensional flow cytometry, single cell genomics and digital pathology, and we are always looking for new cool analytical pipelines to face the challenge of big-data in immunology. 

    Research support

    We are grateful for the support of:

    • Åke Olsson Foundation
    • Clas Groschinsky Foundation
    • Vetenskapsrådet
    • Karolinska Institutet
    • CIMED
    • Jonas Söderquist Scholarship

    Selected publications

    2021

     

    Natural killer cells and unconventional T cells in COVID-19
    Björkström NK and Ponzetta A. Current Opinion on Virology (2021)

    A biliary immune landscape map of primary sclerosing cholangitis reveals a dominant network of neutrophils and tissue-resident T cells
    Zimmer CL, von Seth E, Buggert M, Strauss O, Hertwig L, Nguyen S, Wong AYW, Zotter C, Berglin L, Michaëlsson J, Reuterwall-Hansson M, Arnelo U, Sparrelid E, Ellis ECS, Söderholm JD, Keita ÅV, Holm K, Özenci V, Hov JR, Mold JE, Cornillet M, Ponzetta A, Bergquist A, and Björkström NK. Science Translational Medicine (2021)

    High-dimensional profiling reveals phenotypic heterogeneity and disease-specific alterations of granulocytes in COVID-19.
    Lourda M#, Dzidic M#, Hertwig L#, Bergsten H, Palma Medina LM, Kvedaraite E, Chen P, Muvva JR, Gorin JB, Cornillet M, Emgård J, Moll K, García M, Maleki KT, Klingström J, Michaëlsson J, Flodström-Tullberg M, Brighenti S, Buggert M, Mjösberg J, Malmberg KJ, Sandberg JK, Henter JI, Folkesson E, Gredmark-Russ S, Sönnerborg A, Eriksson LI, Rooyackers O, Aleman S, Strålin K, Ljunggren HG, Björkström NK, Svensson M, Ponzetta A*, Norrby-Teglund A*, Chambers BJ*; and the Karolinska KI/K COVID-19 Study Group. Medrxiv (2021) #/*equal contribution

    Complement activation promoted by the lectin pathway mediates C3aR-dependent sarcoma progression and immunosuppression.
    Magrini E, Di Marco S, Mapelli S, Perucchini C, Pasqualini F, Donato A, de la Luz Guevara Lopez M, Carriero R, Ponzetta A, Colombo P, Cananzi F, Supino D, Reis ES, Peano C, Inforzato A, Jaillon S, Doni A, Lambris JD, Mantovani A, Garlanda C. Nature Cancer (2021)

    Major alterations in the mononuclear phagocyte landscape associated with COVID-19 severity.
    Kvedaraite E, Hertwig L, Sinha I, Ponzetta A, Myrberg IH, Lourda M, Dzidic M, Akber M, Klingström J, Folkesson E, Muvva JR, Chen P, Brighenti S, Norrby-Teglund A, Eriksson LI, Rooyackers O, Aleman S, Strålin K, Ljunggren HG, Ginhoux F, Björkström NK, Henter JI, Svensson M, Karolinska COVID-19 Study Group. PNAS (2021)

    2020

     

    MAIT cell activation and dynamics associated with COVID-19 disease severity and outcome.
    Parrot T*, Gorin JB*, Ponzetta A, Maleki KT, Kammann T, Emgård J, Perez-Potti A, Sekine T, Rivera-Ballesteros O, the Karolinska COVID-19 Study Group, Folkesson E, Rooyackers O, Eriksson LI, Norrby-Teglund A, Ljunggren HG, Björkström NK, Aleman S, Buggert M, Klingström J, Strålin K, and Sandberg JK.  Science Immunology (2020)

    Natural killer cell immunotypes related to COVID-19 disease severity.
    Maucourant C*, Filipovic I*, Ponzetta A*, Aleman S, Cornillet M, Hertwig L, Strunz B, Lentini A, Reinius B, Brownlie B, Cuapio Gomez A, Ask EH, Hull RM, Haroun-Izquierdo A, Schaffer M, Klingström J, Folkesson E, Buggert M, Sandberg JK, Eriksson LI, Rooyackers O, Ljunggren HG, Malmberg KJ, Michaëlsson J, Marquardt N, Hammer Q, Strålin K, Björkström NK; and the Karolinska COVID-19 Study Group. ​​​​​​​Science Immunology (2020) *equal contribution.

    Neutrophil diversity and plasticity in tumour progression and therapy.
    Jaillon S, Ponzetta A, Di Mitri D, Santoni A, Bonecchi R, Mantovani A
    Nature Reviews Cancer 2020 09;20(9):485-503

    2015-2019

    The Atypical Receptor CCRL2 Is Essential for Lung Cancer Immune Surveillance.
    Del Prete A, Sozio F, Schioppa T, Ponzetta A, Vermi W, Calza S, Bugatti M, Salvi V, Bernardini G, Benvenuti F, Vecchi A, Bottazzi B, Mantovani A, Sozzani S. Cancer immunology research (2019)

    Neutrophils driving unconventional T cells mediate resistance against murine sarcomas and selected human tumors.
    Ponzetta A, Carriero R, Carnevale S, Barbagallo M, Molgora M, Perucchini C, Magrini E, Gianni F, Kunderfranco P, Polentarutti N, Pasqualini F, Di Marco S, Supino D, Peano C, Cananzi F, Colombo P, Pilotti S, Alomar SY, Bonavita E, Galdiero MR, Garlanda C, Mantovani A, Jaillon S. Cell (2019)

    IL-1R8 is a checkpoint in NK cells regulating anti-tumour and anti-viral activity.
    Molgora M, Bonavita E, Ponzetta A, Riva F, Barbagallo M, Jaillon S, Popović B, Bernardini G, Magrini E, Gianni F, Zelenay S, Jonjić S, Santoni A, Garlanda C, Mantovani A. ​​​​​​​Nature (2017)

    Multiple Myeloma Impairs Bone Marrow Localization of Effector Natural Killer Cells by Altering the Chemokine Microenvironment.
    Ponzetta A, Benigni G, Antonangeli F, Sciumè G, Sanseviero E, Zingoni A, Ricciardi MR, Petrucci MT, Santoni A, Bernardini G
    Cancer Res 2015 Nov;75(22):4766-77

    Full list of publications