Andrea Ponzetta team – 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 research group at the Center of Infectious Medicine (CIM).

About our research

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

Senior research specialist
H7 Department of Medicine, Huddinge

Andrea joined CIM in 2020. He is currently interested in the biology of innate-like lymphocytes and in their impact in human tumors. 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. When not at work, Andrea enjoys travelling, cooking and hiking.

 

Group members

Itzel Medina Andrade

Postdoctoral studies
H7 Department of Medicine, Huddinge

Itzel Medina received her PhD in Biomedical Sciences in 2021 at Universidad Nacional Autónoma de México, UNAM- FES-Iztacala in México. Her research project was focused on the impact of IL-4Rα expression in macrophages during inflammation-associated colon cancer. Itzel was also involved in other projects, such as the study of Tregs in colon cancer and of taenia crassiceps antigens as modulators of inflammation. In her spare time Itzel enjoys drawing, listening to music, reading classic novels, and visiting new places. Also, she now loves Fika.

H7 Department of Medicine, Huddinge

In 2022 Rebecca started her PhD studies in Andrea Ponzetta team, where she is studying dynamic alterations of the immune landscape in gastroesophageal cancer.

Rebecca obtained her MSc degree in Biomedicine from Karolinska Institutet in 2021. She performed her MSc thesis project in Petter Höglund's research group where she studied the role of FOXO1 and FOXO3 in NK-cell maturation and function. In 2021-2022 she worked in the Cell Profiling team at SciLifeLab, with professor Emma Lundberg. As part of the Cell Atlas team, she focused on mapping subcellular protein localization for the Human Protein Atlas project. She also worked within the ESPACE initiative where she performed spatial proteomic analysis of healthy pancreas tissue using the Phenocycler system from Akoya.

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; andrea.ponzetta@ki.se

Collaborations

Our research at the Center for Infectious Medicine (CIM) 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:

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

Selected publications

  1. Imprint of unconventional T-cell response in acute hepatitis C persists despite successful early antiviral treatment.
    Du Y, Khera T, Strunz B, Deterding K, Todt D, Woller N, Engelskircher SA, Hardtke S, Port K, Ponzetta A, Steinmann E, Cornberg M, Hengst J, Björkström NK, Wedemeyer H, Eur J Immunol 2022 03;52(3):472-483
     
  2. 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)
     
  3. 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, Sinha I, 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*; Karolinska KI/K COVID-19 Study Group. PNAS (2021) *equal contribution.
     
  4. 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)
     
  5. 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)
     
  6. 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.
     
  7. 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).
     
  8. 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)
     
  9. 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)
     
  10. 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 Research (2015)

Full list of publications

Full list of publications