Mye-EUNITER
 

Sica, Antonio

Antonio Sica's group is focused on the investigation of inflammatory circuits and molecules expressed within the tumor microenvironment and their role in tumor progression. Within this scenario, the laboratory also investigates myelopoietic pathways associated with tumor development and their relation to disease progression. The cellular and molecular phenotype of Tumor-Associated macrophages (TAM) and myeloid-derived suppressor cells (MDSC) is analysed, along with tumor-derived factors and microenvironmental conditions, including hypoxia, guiding their pro-tumoral differentiation. Available experimental models include transplantable, chemically-induced and spontaneous tumor models. In collaboration with other institutions, high-throughput screenings (generation of phosphorylation maps, RNASeq, ChipSeq) are performed in the perspective to identify and validate in specimens from cancer patients selected molecules as potential prognostic and therapeutic targets.

Models available:

Different total and conditional KO mouse models targeting the myeloid compartment. Different chemically-induced and spontaneous models of mouse tumors.

Cells available:

Macrophages and myeloid derived suppressor cells.

Questions:

  • Myeloid cell biology
  • Mechanisms by which tumors reprogram myeloid cell differentiation and functions, towards a tumor promoting mode
  • Identification of new therapeutic targets and validation in preclinical models of cancer, alone and in combination with established protocols of immunotherapy
  • Identification of clinical response markers to immunotherapy treatments

Technology available:

Genomic (RNASeq, ChipSeq, methylation analysis) and proteomic analysis, lipidomic analysis (collaboration),  engineered mouse models, cytofluorimetry, confocal microscopy.

Key publications related to Mye-EUNITER:

  1. Strauss L, Sangaletti S, Consonni FM, Szebeni G, Morlacchi S, Totaro MG, Porta C, Anselmo A, Tartari S, Doni A, Zitelli F, Tripodo C, Colombo MP, Sica A. RORC1 Regulates Tumor-Promoting "Emergency" Granulo-Monocytopoiesis. Cancer Cell. 2015 Aug 10;28(2):253-69.
  2. Ries CH, Cannarile MA, Hoves S, Benz J, Wartha K, Runza V, Rey-Giraud F, Pradel LP, Feuerhake F, Klaman I, Jones T, Jucknischke U, Scheiblich S, Kaluza K, Gorr IH, Walz A, Abiraj K, Cassier PA, Sica A, Gomez-Roca C, de Visser KE, Italiano A, Le Tourneau C, Delord JP, Levitsky H, Blay JY, Rüttinger D. Targeting tumor-associated macrophages with anti-CSF-1R antibody reveals a strategy for cancer therapy. Cancer Cell. 2014 Jun 16;25(6):846-59.
  3. Sica A, Mantovani A. Macrophage plasticity and polarization: in vivo veritas. J Clin Invest. 2012 Mar;122(3):787-95.
  4. Porta C, Rimoldi M, Raes G, Brys L, Ghezzi P, Di Liberto D, Dieli F, Ghisletti S, Natoli G, De Baetselier P, Mantovani A, Sica A. Tolerance and M2 (alternative) macrophage polarization are related processes orchestrated by p50 nuclear factor kappaB. Proc Natl Acad Sci U S A. 2009 Sep 1;10 (35):14978-83.
  5. Biswas SK, Gangi L, Paul S, Schioppa T, Saccani A, Sironi M, Bottazzi B, Doni A, Vincenzo B, Pasqualini F, Vago L, Nebuloni M, Mantovani A, Sica A. A distinct and unique transcriptional program expressed by tumor-associated macrophages (defective NF-kappaB and enhanced IRF-3/STAT1 activation). Blood. 2006 Mar 1;107(5):2112-22.

Contact details:

Department of Pharmacological Sciences
University of Eastern Piedmont
Novara
Italy

Humanitas Clinical and Research Center
Rozzano
Milan
Italy

Tel: +39 0321 375881
Fax: +39 0321 375621
antonio.sica@humanitasresearch.it 
antonio.sica@uniupo.it