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 ideally located at the crossroad between innate and adaptive immunity: unconventional T cells (UTC). Over the last two decades, a non-redundant role for UTC has been demonstrated in countless physiological and pathological contexts, generating a growing interest in their potential therapeutic application. However, several fundamental aspects of UTC biology and function remain elusive.
One of our research questions stems from our findings on a poorly characterised UTC population (DNT⍺β cells) displaying a prominent antitumor activity in preclinical models (Ponzetta et al, Cell 2019). As the immunomodulatory function of DNT⍺β cells in the human setting is completely unknown, our team is dissecting human DNT⍺β composition and behavior from multiple perspectives, both in peripheral blood and in tissues.
In parallel, our team is evaluating the functional implications and the translational value of the UTC compartment in the tumor setting, and specifically in gastroesophageal adenocarcinoma (GEAC). GEAC is a heterogeneous disease with low survival rate and increasing incidence in western countries, where conventional therapy has limited efficacy. Our objective is to use immune parameters to improve the current patient classification and find new therapeutic targets, as a fundamental step towards personalized treatment.
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 and integrate a range of single cell technologies, including high-dimensional flow cytometry, single cell genomics and digital pathology, and we are always looking for new analytical pipelines to face the challenge of big-data in immunology.
Team leader
Andrea Ponzetta
Senior research specialistAndrea 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 studiesItzel 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. She 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.
Rebecca Maltez De Sousa
PhD studentIn 2021 Rebecca obtained her MSc degree in Biomedicine from Karolinska Institutet. She performed her MSc thesis project in Petter Höglunds 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. In 2022 Rebecca started her PhD studies in Andrea Ponzetta team where she is studying dynamic alterations of the immune landscape in gastroesophageal cancer.
As a research assistant, Kejsi is involved in various experimental work focusing on the characterization of the immune response in the context of gastroesophageal adenocarcinoma (GEAC). Kejsi recently obtained her MSc degree in Medical Biotechnology from the University of Trieste, Italy. As part of it, she performed her thesis project at the Medical Inflammation Research group. Her project focused on identifying new candidates of a peptide-based tolerogenic vaccine for Rheumatoid Arthritis. Kejsi likes to spend her spare time reading, travelling, and cooking.
Open positions
We always want to get in touch with talented potential co-workers with questions on unconventional T cells and tumor immunology. If you are interested in joining our team, please contact the Team Leader 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:
- Cancerfonden
- Sjöbergstiftelse
- Radiumhemmet Forskningsfonder
- KID-Funding
- Åke Olsson Foundation
- Clas Groschinsky Foundation
- Vetenskapsrådet
- Karolinska Institutet
- CIMED
- Jonas Söderquist Scholarship
Selected publications
- 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
- 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, 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.
- 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)
- 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).
- 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 Research (2015)