Research Group

Di Mitri Group

Tumor Microenvironment Lab

Di Mitri Group

Diletta Di Mitri

Junior Group Leader

Our lab investigates the mechanisms exploited by tumors to evade the immune response and to re-educate the immune infiltrate in its favor, by combining multi-parametric flow cytometry, spatial multiomics approaches and advanced RNA sequencing.

The challenge

The tumor microenvironment (TEM) is a complex ecosystem of different types of cells and tissues that surround the tumor and under its molecular signaling sustain its growth and progression. There is extensive evidence that within this microenvironment, cancer cells are able to reprogram the immune system towards pro-tumoral behaviors, as proven by the efficacy of immune-checkpoint inhibitors and immunecell-based therapies. However, we still know very little about the crosstalk between cancer and the immune system in the tumor microenvironment. In these unknown interactions – that thanks to new technologies we can now describe with unprecedented detail – hide precious insights for the development of novel immunotherapy strategies.

Main research areas

Profiling of tumor-associated macrophages in cancer

To better understand the mechanisms underlying immune evasion and leading to tumor progression and resistance to therapy in prostate cancer and melanoma, we are profiling the immune microenvironment in urogenital tumors and and melanoma by mean of FACS and transcriptomic analysis, at different progression stages. In a recent study, we uncovered the infiltration of a subset of macrophages that accumulates lipids, shows pro-tumoral features and supports cancer invasion. We also identified the scavenger receptor involved in the lipids intake and demonstrated that its inhibition in-vivo reduces tumor growth and invasiveness.

NK cells impairment and NK-based cell therapies in solid tumors

Natural killer (NK) cells are a specialized population of immune cells that mediates cytotoxic action against damaged, infected and tumor cells. Our lab investigates the crosstalk between cancer and NK cells, both in vitro and ex vivo. We are applying high dimensional approaches to explore their spatial localization, phenotype and transcriptional landscape in urogenital cancers and melanoma, and we are testing the proof of concept of new NK-based cell therapies that overcome the mechanisms leveraged by the tumor to impair NK cells action.

Immune-profiling of cancer patients

We combine multi-parametric flow cytometry, spatial proteomic analysis and RNA sequencing approaches to provide a comprehensive characterization at single cell level of the immune landscape in cancer patients. We are investigating the cell dynamics within the tumor immune microenvironment and at the periphery to unveil mechanisms that drive and predict tumor progression and resistance to therapies.

Selected publications

Di Mitri D
J Exp Med
Macrophages and bone metastasis.
Alvisi G
J Hepatol
Multimodal single-cell profiling of intrahepatic cholangiocarcinoma defines hyperactivated Tregs as a potential therapeutic target.
Marelli G
J Immunother Cancer
Lipid-loaded macrophages as new therapeutic target in cancer.
Masetti M
J Exp Med
Lipid-loaded tumor-associated macrophages sustain tumor growth and invasiveness in prostate cancer.
Jaillon S
Nat Rev Cancer
Neutrophil diversity and plasticity in tumour progression and therapy.
Di Mitri D
Cell Rep
Re-education of Tumor-Associated Macrophages by CXCR2 Blockade Drives Senescence and Tumor Inhibition in Advanced Prostate Cancer.
Calcinotto A
Nature
IL-23 secreted by myeloid cells drives castration-resistant prostate cancer.
Chen J
Nat Genet
Compartmentalized activities of the pyruvate dehydrogenase complex sustain lipogenesis in prostate cancer.
Di Mitri D
Immunology
The p38 mitogen-activated protein kinase cascade modulates T helper type 17 differentiation and functionality in multiple sclerosis.
Di Mitri D
Nature
Tumour-infiltrating Gr-1+ myeloid cells antagonize senescence in cancer.
Di Mitri D
J Immunol
Reversible senescence in human CD4+CD45RA+CD27- memory T cells.

Group members

Di Mitri Group
Diletta Di Mitri

Junior Group Leader

Di Mitri Group
Giulia Marelli

Postdoc fellow

Di Mitri Group
Marta Pandini

PhD student

Di Mitri Group
Federica Portale

Postdoc fellow