FIGHT-CANCER

Long non-coding RNAs of tumor infiltrating lymphocytes as novel anti-cancer therapeutic targets

Coordinatore	FONDAZIONE ISTITUTO NAZIONALE DI GENETICA MOLECOLARE INGM    more Spiacenti, non ci sono informazioni su questo coordinatore. Contattare Fabio per maggiori infomrazioni, grazie.
Nazionalità Coordinatore	Italy [IT]
Totale costo	1˙998˙000 €
EC contributo	1˙998˙000 €
Programma	FP7-IDEAS-ERC Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)
Code Call	ERC-2013-CoG
Funding Scheme	ERC-CG
Anno di inizio	2014
Periodo (anno-mese-giorno)	2014-04-01   -   2019-03-31

 Partecipanti

#	participant	country	role	EC contrib. [€]
1	FONDAZIONE ISTITUTO NAZIONALE DI GENETICA MOLECOLARE INGM  Organization address address: Via Francesco Sforza 35 city: MILANO postcode: 20122 contact info Titolo: Dr. Nome: Massimiliano Cognome: Pagani Email: send email Telefono: +39 02 00660322 Fax: +39 02 00660216	IT (MILANO)	hostInstitution	1˙998˙000.00
2	FONDAZIONE ISTITUTO NAZIONALE DI GENETICA MOLECOLARE INGM  Organization address address: Via Francesco Sforza 35 city: MILANO postcode: 20122 contact info Titolo: Mr. Nome: Stefano Cognome: Apollonio Email: send email Telefono: +39 02 00660209 Fax: +39 02 00660216	IT (MILANO)	hostInstitution	1˙998˙000.00

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 Obiettivo del progetto (Objective)

'Although tumor tissues can be infiltrated by T cells specific for tumor antigens, the effector functions of these lymphocytes are generally suppressed by CD4 regulatory T cells (Tregs). Since tumor infiltrating Tregs can display function heterogeneity, depending on both the tumor type and the inflammatory milieu, only inhibition of the right Treg activity should result in the unleash of an effective anti-tumor T cell responses. Experimental plan: To identify the Tregs that truly inhibit anti-tumor T cells, we will profile by RNA-Seq the transcriptome of Tregs infiltrating both tumor and healthy tissues. In particular, we will focus on LncRNAs and the gene networks they modulate, since they have recently emerged as relevant epigenetic regulators of cell differentiation and identity. We will exploit this new knowledge to create a panel of regulatory transcripts, which will be assessed at single cell level on tumor infiltrating Tregs, so to determine the association of specific transcripts with different Treg populations. Since downregulation of specific lncRNAs might be an efficient way to inhibit the “unwanted” Tregs at tumor sites, we aim at targeting lncRNAs uniquely expressed in these Tregs and propose to develop AsiCs, chimeric molecules composed by an aptamer, single stranded oligonucleotides that bind to cell surface markers, and a siRNA, short RNAs downregulating specific lncRNAs. Deliverables and conclusions: this proposal will provide new knowledge on tumor infiltrating Tregs possibly allowing definition of molecular signatures of Tregs with either positive or negative effects on antitumor T cell responses. Moreover, we will develop new molecules that specifically target lncRNAs of interest and that will help identifying new antitumor therapeutic targets. In conclusion, the possibility to modulate Tregs effector functions may not only offer new anti-tumor therapy but more in general may be relevant to any immunomodulatory therapeutic strategies.'