Biography
As a young student, I have always been fascinated by the complexity of nature and I found myself amazed when I have started studying the immune system and its unique combination of elegance and efficacy. For this reason, once I completed my master in Biotechnology, I enthusiastically joined the Immunological Science program at the University of Rome as a graduate student. In the laboratory directed by Angela Santoni, I have studied how two populations of immune cells, T cells and NK cells, interact with each other in the human system. As most of my academic education took place in Italy, I decided to move to the US for my post-doctoral training, and in 2010 I joined the group of David Raulet at the University of California, Berkeley. In David’s lab, I have investigated the mechanisms that underlie the failure of the immune response to tumors. My time in Berkeley was precious and I received an excellent training in tumor immunology. I published several high profile papers and I became an expert in the immuno-oncology field. In 2016, I was recruited by a joint effort of the University of Ottawa and the Ottawa Hospital Research Institute to lead a group in cancer immunology. My laboratory is interested in understanding the complex interactions between immune cells and tumors to find new ways to harness the immune system against cancer.
Research Interests
The immune system is an incredible weapon against tumors and yet, cancer is still one of the leading causes of death. It is of extreme importance to have a more detailed knowledge of the complex interactions between immune cells and cancer in order to design more tailored and effective immunotherapies. My group is interested in understanding why a subset of immune cells named Natural Killer (NK) cells are often unable to kill tumor cells and to find new ways to harness the activity of NK cells against cancer.
Research Activities
- Tumor Immunology: We are interested in the basic mechanisms that govern the immune response to cancer, with a particular focus on Natural Killer cells. We are currently investigating why Natural Killer cells fail to eliminate tumors. We are studying the contribution of checkpoint receptors, such as PD-1 and LAG-3, in suppressing NK cell responses. We are also interested in the crosstalk between Natural Killer cells and immuno-modulatory cells, such as Tregs and MDSCs.
- Oncolytic Virotherapy: Oncolytic viruses represent an innovative solution for cancer immunotherapy. We are interested in studying how oncolytic viruses modulate the immune response and design novel viruses with improved anti-tumor efficacy.
- The Immunoprofile Effort: In collaboration with surgeons at The Ottawa Hospital, we are profiling the phenotype and function of immune cells in human cancer using high end flow cytometry and single cell RNA-sequencing.
- Screens: We are conducting a number of screens to understand the biological mechanisms that regulate expression and function of checkpoint receptors.
Selected Top Publications
- Hsu J.+, Hodgins J.J.+, Marathe M., Nicolai C.J., Bourgeois-Daigneault M.C., Trevino T.N., Azimi C.S., Scheer A.K., Randolph H.E., Thompson T.W., Zhang L., Iannello A., Mathur N., Jardine K.E., Kirn G.A., Bell J.C., McBurney M.W., Raulet D.H.*, Ardolino M.* Contribution of NK cells to immunotherapy mediated by PD-1/PD-L1 blockade. The Journal of Clinical Investigation, 2018, 128(10):4654-4688. *co-corresponding authors and co-senior authors
- Hodgins J.J., Khan S.T., Park M., Auer R.C., Ardolino M. Killers 2.0: NK Cell Therapies at the Forefront of Cancer Control. The Journal of Clinical Investigation, 2019, 129(9):3499-3510
- Al-Zahrani K., Abou-Hamad J., Pryce B., Cook D., Hodgins J.J., Labreche C., Robineau‑Charette P., de Souza C., Bell J.C., Auer R.C., Ardolino M., Vanderhyden B., Sabourin L. Loss of Ste20-like kinase induces a basal/stem-like phenotype in HER2-positive breast cancers. Oncogene, in press
- Ardolino M., Azimi C.S., Iannello A., Trevino T.N., Horan L., Zhang L., Deng W., Ring A. Fischer S., Garcia K.C., Raulet D.H. Cytokine therapy reverses NK cell anergy in MHC-deficient tumors. The Journal of Clinical Investigation, 2014, 124 (11):4781-94
- Ardolino M., Zingoni A., Cerboni C., Cecere F., Soriani A., Iannitto M.L., Santoni A. DNAM-1 ligands expression on Ag-stimulated T lymphocytes is mediated by ROS-dependent activation of DNA-damage response: relevance for NK-T-cell interaction. Blood, 2011, 117 (18); 4778-86
All other Publications
- Cerboni C., Ardolino M., Santoni A, Zingoni A. Detuning CD8+ T lymphocytes by down-regulation of the activating receptor NKG2D: role of NKG2D ligands released by activated T cells. Blood, 2009, 113; 2955-64
- Zingoni A., Cerboni C., Ardolino M., Santoni A. Modulation of T-cell mediated immune responses by Natural Killer cells (Chapter 17). in J. Zimmer (Ed): Natural Killer Cells, at the forefront of modern immunology. Springer, 2010
- Ardolino M., Zingoni A., Cerboni C., Cecere F., Soriani A., Iannitto M.L., Santoni A. DNAM-1 ligands expression on Ag-stimulated T lymphocytes is mediated by ROS-dependent activation of DNA-damage response: relevance for NK-T-cell interaction. Blood, 2011, 117 (18); 4778-86
- Zingoni A., Ardolino M., Santoni S., Cerboni C. NKG2D and DNAM-1 activating receptors and their ligands in NK-T cell interactions: role in the NK cell-mediated negative regulation of T cell responses. Frontiers in Immunology, 2013, 3; 408
- Sheppard S., Triulzi C., Ardolino M., Serna D., Raulet D.H., Guerra N. Characterization of a novel NKG2D and NKp46 double-mutant mouse reveals subtle variations in the NK cell repertoire. Blood, 2013, 121 (25); 5025-33
- Iannello A., Thompson T.W., Ardolino M., Lowe S.W., Raulet D.H. p53-dependent chemokine production by senescent tumor cells supports NKG2D-dependent tumor elimination by natural killer cells. The Journal of Experimental Medicine, 2013, 210 (10); 2057-69
- Bekerman E., Jeon D., Ardolino M., Coscoy L. A role for host activation-induced cytidine deaminase in innate immune defense against KSHV. Plos Pathogens, 2013, 9 (11); e1003748
- Marcus A., Gowen B.G., Thompson T., Iannello A., Ardolino M., Deng W., Wang L., Shifrin N., Raulet D.H. Recognition of tumors by the innate immune system and natural killer cells. Advances in Immunology, 2014, 122:91-128
- Shifrin N., Raulet D.H., Ardolino M. NK cell tolerance, responsiveness and missing self recognition. Seminars in Immunology, 2014, 26 (2):138-44
- Ardolino M., Azimi C.S., Iannello A., Trevino T.N., Horan L., Zhang L., Deng W., Ring A. Fischer S., Garcia K.C., Raulet D.H. Cytokine therapy reverses NK cell anergy in MHC-deficient tumors. The Journal of Clinical Investigation, 2014, 124 (11):4781-94
- Ardolino M., Hsu J., Raulet D.H. Cytokine treatment in cancer immunotherapy. Oncotarget, 2015, 14; 6(23): 1936-7
- Iannello A., Thompson T.W., Ardolino M., Marcus A., Raulet D.H. Immunosurveillance of tumors by innate immune cells. Current Opinion in Immunology, 2016, 38: 52-8
- Ardolino M., Raulet D.H. Cytokine therapy restores anti-tumor responses of NK cells rendered anergic in MHC I-deficient tumors. Oncoimmunology, 2016, 5(1): e1002725
- Spiegel A., Houshyar S., Brooks M., Reinhardt F., Ardolino M., Fessler E., DeCock J., Zervantonakis I. K., Ng Eaton E., Iwamoto Y., Cortez-Retamozo V., Pittet M. K., Raulet D. H., Weinberg R.A. Neutrophils suppress intraluminal NK tumor cell clearance and enhance extravasation. Cancer Discovery, 2016, 6(6): 630-49
- Tovbis Shifrin N., Kissov D.U.*, Ardolino M.*, Joncker N., Raulet D.H. Differential role of hematopoietic and nonhematopoietic cell types in the regulation of NK cell tolerance and responsiveness. The Journal of Immunology, 2016, 197(10):4127-36 * Equal contribution