The research interest of the group is focused on the study of the tumor microenvironment. The aim is to develop innovative myeloid-modulating strategies that will permit to improve the immunotherapeutic approaches against cancer. We contributed to the definition and characterization of immunoregulatory cells of myeloid origin, called myeloid-derived suppressor cells (MDSCs) whose negative influence on anti-tumor immunity represents an obstacle to successful immunotherapy of cancer. We are now investigating the spatial and functional interactions between tumor cells, immune cells and the extracellular matrix in in vivo murine models and human tumors to develop innovative therapies that aim at limiting the immunosuppressive role of MDSCs and macrophages on anticancer T cell response and will be used in combination with cell therapy or immune checkpoint inhibitors. Taking advantage of several international collaborations with nanomedicine experts, we are also optimizing innovative drugs and delivery systems easily transposable to the clinic.

Five Selected Publications:

• Peranzoni E, Ingangi V, Masetto E, Pinton L, Marigo I. Myeloid Cells as Clinical Biomarkers for Immune Checkpoint Blockade. Front Immunol. 2020 Jul 24;11:1590. doi: 10.3389/fimmu.2020.01590.
• Marigo I, Trovato R, Hofer F, Ingangi V, Desantis G, Leone K, De Sanctis F, Ugel S, Canè S, Simonelli A, Lamolinara A, Iezzi M, Fassan M, Rugge M, Boschi F, Borile G, Eisenhaure T, Sarkizova S, Lieb D, Hacohen N, Azzolin L, Piccolo S, Lawlor R, Scarpa A, Carbognin L, Bria E, Bicciato S, Murray PJ, Bronte V. Disabled Homolog 2 Controls Prometastatic Activity of Tumor-Associated Macrophages. Cancer Discov. 2020 Nov;10(11):1758-1773. doi: 10.1158/2159-8290.CD-20-0036.
• Marigo I, Zilio S, Desantis G, Mlecnik B, Agnellini AH, Ugel S, Sasso MS, Qualls JE, Kratochvill F, Zanovello P, Molon B, Ries CH, Runza V, Hoves S, Bilocq AM, Bindea G, Mazza EM, Bicciato S, Galon J, Murray PJ, Bronte V. T Cell Cancer Therapy Requires CD40-CD40L Activation of Tumor Necrosis Factor and Inducible Nitric-Oxide-Synthase-Producing Dendritic Cells. Cancer Cell. 2016 Sep 12;30(3):377-90.
• Sasso MS, Lollo G, Pitorre M, Solito S, Pinton L, Valpione S, Bastiat G, Mandruzzato S, Bronte V, Benoit JP, Marigo I. Low dose gemcitabine-loaded lipid nanocapsules target monocytic myeloid-derived suppressor cells and potentiate cancer immunotherapy. Biomaterials. 2016 Jul;96:47-62.
• Marigo I, Bosio E, Solito S, Mesa C, Fernandez A, Dolcetti L, Ugel S, Sonda N, Bicciato S, Falisi E, Calabrese F, Basso G, Zanovello P, Cozzi E, Mandruzzato S, Bronte V. Tumor-induced tolerance and immune suppression depend on the C/EBPbeta transcription factor. Immunity. 2010 Jun 25;32(6):790-802.

Active Funding:

Bandi intramurali 5x1000 IOV-IRCCS (2019-2023). MACROMONDO: “Macrophage-assisted metastatic process is controlled by a specific endocytic pathway”.
EURONANOMED (2020-2022). NanoNET: “Targeting breast tumors with anti-Netrin-1 nanocarriers as a promoter of immunity”.
Bandi intramurali 5x1000 IOV-IRCCS (2020-2023). SENTINEL: “Analysis of lymphocytes in glioblastoma patients to define the immunosuppressive state and potential response to immunotherapy”.
EURONANOMED (2022- 2024). RAIN: “Radiotherapy-Activated Immunomodulating Niches”.

People Involved:
Ilaria Marigo, PhD, Assistant Professor (RTDb)

Group members:
Elisa Peranzoni, PhD, Researcher (IOV-IRCCS)
Vincenzo Ingangi, Post-Doc (IOV-IRCCS)
Diana Marcela Hernandez Palomino, PhD Student (DiSCOG)