Research

Human tumor immunology

The research activity of the laboratory of human tumor immunology is focused on the study of immune evasion mechanisms of myeloid cells in cancer patients. The role of these cells in tumor progression is mainly studied in the context of primary brain tumors, characterized by a large myeloid infiltrate with profound immunosuppressive and pro-tumoral activities. Understanding the mechanisms of local and systemic immune suppression is a first necessary step to develop novel immunotherapy strategies that combine the stimulation of an efficient anti-tumor immune response with a therapy targeting immune suppressive mechanisms. In addition, we integrate the immunophenotyping data of the tumor microenvironment with the neuroimaging data obtained by MR, with the aim to localize immune suppressive cell infiltrates in different tumor and perilesional regions.

Specifically, the main research interests of the laboratory are:

  • Role of circulating and tumor-associated myeloid-derived suppressor cells (MDSCs) in the immune evasion in cancer patients.
  • Evaluation of new nanomedicines as drug delivery systems targeting myeloid suppressive and tumor cells.
  • Study of the innate immune response in primary brain cancer patients: evaluation of the function of circulating and tumor-associated myeloid cells.
  • Analysis and imaging by MR of the role of iron metabolism in the immune suppressive activity of tumor-associated macrophages

5 selected publications:

Magri S, Musca B, Pinton L, Orecchini E, Belladonna ML, Orabona C, Bonaudo C, Volpin F, Ciccarino P, Baro V, Della Puppa A, Mandruzzato S. The immunosuppression pathway of tumor-associated macrophages is controlled by heme oxygenase-1 in glioblastoma patients. International Journal of Cancer. 2022 Sep 2.

Pinton L, Masetto E, Vettore M, Solito S, Magri S, D'Andolfi M, Del Bianco P, Lollo G, Benoit JP, Okada H, Diaz A, Della Puppa A, Mandruzzato S. The immune suppressive microenvironment of human gliomas depends on the accumulation of bone marrow-derived macrophages in the center of the lesion. Journal for Immunotherapy of Cancer. 2019 Feb 27;7(1):58.

Pinton L, Magri S, Masetto E, Vettore M, Schibuola I, Ingangi V, Marigo I, Matha K, Benoit JP, Della Puppa A, Bronte V, Lollo G, Mandruzzato S. Targeting of immunosuppressive myeloid cells from glioblastoma patients by modulation of size and surface charge of lipid nanocapsules. Journal of Nanobiotechnology. 2020 Feb 17;18(1):31.

Mandruzzato, S., Brandau S., Britten C.M., Bronte V., Damuzzo V., Gouttefangeas C., Maurer D., Ottensmeier C.H., Van der Burg S., Welters M.J.P., Walter S. Towards harmonized phenotyping of human myeloid-derived suppressor cells by flow cytometry: results from an interim study. Cancer Immunology Immunotherapy. 2016 Feb;65(2):161

Solito, S., Falisi, E., Diaz-Montero, CM., Doni, A., Pinton, L., Rosato, A., Francescato, S., Basso, G., Zanovello, P., Oniescu, G., Garrett-Mayer, E., Montero, AJ., Bronte, V., Mandruzzato, S. A human promyelocytic-like population is responsible for the immune suppression mediated by myeloid-derived suppressor cells. Blood, 2011;118(8):2254-65.

Funding:

-AIRC Investigator Grant IG 2016. Project title: “Unveiling the role of myeloid-derived suppressor cells in checkpoint blockade therapy”. € 245.000 (2016-2018)

-TRANSCAN-2, ERA-NET, IMMUNOGLIO: “Immunology and immunotherapy of cancer: strengthening the translational aspects”. Project title: Deciphering immune response against Glioblastoma to find new Targets. Acronym: Immunoglio.  € 300.000 (2017-2019)

-Progetto di Ricerca di Ateneo: bando 2017. Project title: “The dynamic flow of myeloid cells in cancer patients ". € 30.000 (2018-2019)

-Progetto integrato per la Ricerca interdipartimentale DiSCOG, Bando BIRD 2020. Project title “Exploring the role of iron metabolism in tumor-associated macrophages”. € 50.000 (2020-2022)

- IOV-IRCCS Intramural Research Funding Programs 5x1000 2019. Project title “Evaluation of the role of iron metabolism in glioblastoma patients as a new target of intervention and as an imaging tool”.  € 250.000 (2020-2022)

- Ricerca Sanitaria Finalizzata, Ministero della salute, Bando 2019. Project title “An integrative approach to identify immune suppressive features in glioma patients “. € 447,750.000 (2020-2023)

-IOV-IRCCS Intramural Research Funding Programs 5x1000, Project Liquid Biopsy. € 135.000

Group members:

Fellows: Greta Battaggia, Beatrice Musca, Maria Giovanna Russo
PhD students: Ada Tushe, Giulia de Biasi
Graduate students: Norma Muraro, Maria Grazia Molvetti