Sartoris, Silvia

Models available:

Molecular and metabolic control of adaptive immunity in cancer, immune evasion in cancer: role of myeloid-derived suppressor cells (MDSCs).

Murine transgenic models of pancreas, prostate, breast, colon cancer and melanoma (either knock-in or knock out) or with abnormality in key regulatory pathways of myeloid-derived suppressor cells (MDSCs) development, migration and function. Murine syngeneic ortothopically transplantable model of pancreas, prostate, breast, colon cancer and melanoma.

Human samples (blood, bone marrow, tissues with tumor accompanied by normal counterpart).

Ethical committee permissions for experiments with both mice strains and human material.

Cells available:

Human and mouse Myeloid-derived suppressor cells (MDSCs)

Technology available:

Phenotypical and functional characterization of human and mouse myeloid-derived suppressor cells (MDSCs). In samples of blood, spleen, tumor and bone marrow from patients with different tumor histotype (pancreas adenocarcinoma (PDAC), breast, colon, prostate cancer and melanoma) we investigated the presence of a subset of MDSCs that has been shown to be prognostic. We plan to isolate human MDSC subsets by flow-cell sorting from blood of either cancer patients or healthy donors (HD) to evaluate the presence of specific RNA and miRNA patterns. For this purpose, we have already obtained specific miRNA and mRNA signatures of human MDSCs comparing bone marrow cells and bone marrow cells cultured in vitro with selective cytokine cocktails that induce a MDSC differentiation.

On the mouse frontline, we can follow MDSC accumulation during tumor progression in different autochtonous or transplantable mouse tumor models. In our mouse facility we already have the MMTV-PyMT and TRAMP transgenic mouse models, developing spontaneous mammary and prostate tumors respectively. We recently obtained the transgenic mouse lines LSL-KrasG12D/+; Pdx-1-Cre (KC) and LSL-KrasG12D/+; LSL-Trp53R172H/+; Pdx-1-Cre (KPC), by Dr. David Tuveson (Cold Spring Harbor NY-USA). In addition, we have the transplantable B16, CT26. We can study the trafficking and accumulation of MDSCs in peripheral blood, spleen and tumors. Moreover, we are able to modulate MDSCs by different strategies: chemotherapy, gene silencing, and antibody-mediated depletion. 

Key publications related to Mye-EUNITER:

  1. Sonda N, Simonato F, Peranzoni E, Calì B, Bortoluzzi S, Bisognin A, Wang E, Marincola F, Naldini L, Gentner B, Trautwein C, Sackett SD, Zanovello P, Molon B, Bronte V (2013) miR-142-3p prevents macrophage differentiation during cancer-induced myelopoiesis. Immunity 38:1236-49.

  2. Bronte V, Pittet MJ (2013) The spleen in local and systemic regulation of immunity. Immunity 39:806-18.

  3. Gabrilovich DI, Ostrand-Rosemberg S, Bronte V (2012) Coordinated regulation of myeloid cells by tumors. Nat Rev Immunol 12:253-68.

  4. Ugel S, Peranzoni E, Desantis G, Chioda C, Walter S, Weinschenk T, Ochando JC, Cabrelle A, Mandruzzato S, Bronte V (2012). Immune tolerance to tumor antigens occurs in a specialized environment in the spleen. Cell Rep 2:628-39.

  5. 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 (2010) Tumor-induced tolerance and immune suppression depend on the C/EBPbeta transcription factor. Immunity 32:790-802.