Commensal Bacteria as Therapy for Colorectal Cancer – Microbials 2018

This project is one of the five winners of the call 2018 «Microbials – Direct Use of Micro-Organisms». Project partners: The project stems from a proficient interaction between immunologists, microbiologists, pathologists and clinicians with specific expertise in gastrointestinal (GI) tract diseases, working at different Swiss institutions including Ente Ospedaliero Cantonale, Università della Svizzera Italiana, Ente Ospedaliero Cantonale University of Basel, and University of Zürich, . The pre-existing collaboration between these groups will ensure a successful implementation of the planned research.

Données de projet

Numéro du projet: GRS-062/18
Subside accordé: CHF 460'000
Consentement: 29.10.2018
Durée: 05.2019 - 05.2022
Champs d'activité: Microbials, seit 2016

Direction du projet

PD Dr. Giandomenica Iezzi, Head of Translational Research Lab

Università della Svizzera Italiana

Faculty of Biomedical Science

Via G. Buffi 13

6900 Lugano (Schweiz)

Giandomenica.notexisting@nodomain.comIezzi@eoc.notexisting@nodomain.comch

Abstract

Colorectal cancer (CRC) is among the most frequent tumor types and is a leading cause of cancer-related death. Tumor infiltration by defined types of immune cells has been recently recognized to favor prolonged survival. However, immune cell infiltration spontaneously occurs in a minority of cases (<20%). No therapy enhancing immune cell recruitment into tumor tissues is currently available.
In recent studies we found that some commensal bacteria, normally present in the intestinal flora, the so-called microbiome, have the ability to stimulate tumor cells to produce chemotactic factors capable of attracting immune cells into tumor tissues. Upon analysis of the gut flora composition of human CRC samples, we have identified a group of bacterial species which is associated with high expression of chemokines, high densities of tumor infiltrating cells, and prolonged patients’ survival.
These findings suggest the potential therapeutic relevance of the administration of identified bacteria to increase CRC infiltration by immune cells, thereby improving clinical outcome. In the present project, we aim at selecting the most effective bacterial species and combinations for subsequent clinical application.

Quelles sont les particularités de ce projet?

This the first study evaluating the potential therapeutic application of bacterial species found to be associated with favorable clinical outcome in patients with CRC. The newly developed microbiome-based treatment might represent a valid innovative therapy for patients suffering from CRC, estimated, based on published data, as >1 M patients per year worldwide. Enhancement of immune infiltration in CRC upon bacteria-based therapy is expected to increase recurrence free and overall survival in early stage CRCs. Moreover, in advanced CRC cases, it might improve response rates to standard chemotherapies or emerging immunotherapies.

Etat/résultats intermédiaires

The project will be implemented within the newly established Translational Research group of the Department of Surgery, of the Ente Ospedaliero Cantonale, strategically embedded within the Institute of Research of Biomedicine, in close contact with other groups of prominent oncologists and immunologists. After the initial set-up of the lab, we are now ready to start the in vitro experimental phase.

Publications

Cremonesi E, Governa V, Garzon JFG, Mele V, Amicarella F, Muraro MG, Trella E, Galati-Fournier V, Oertli D, Däster SR, Droeser RA, Weixler B, Bolli M, Rosso R, Nitsche U, Khanna N, Egli A, Keck S, Slotta-Huspenina J, Terracciano LM, Zajac P, Spagnoli GC, Eppenberger-Castori S, Janssen KP, Borsig L, Iezzi G. Gut microbiota modulate T cell trafficking into human colorectal cancer. Gut. 2018 Nov;67(11):1984-1994. doi: 10.1136/gutjnl-2016-313498. Epub 2018 Feb 6.

Revue de presse

None so far

Liens

A video abstract related to the publication indicated above
USI, Faculty of Biomedical Sciences
Ente Ospedaliero Cantonale

Personnes participant au projet

PD Dr. Giandomenica Iezzi Head of Translational Research Lab, Università della Svizzera Italiana, Department of Surgery, Ente Ospedaliero Cantonale and Faculty of Biomedical Science
Prof. Majno-Hurst, Head of the Department of Surgery, Ente Ospedaliero Cantonale Lugano and Chair of Surgery of the Università Svizzera Italiana (USI)
Prof. Dimitri Christoforidis, Deputy Head of the Department of Surgery Ente Ospedaliero Cantonale Lugano, specialized in colorectal surgery
Prof. Adrian Egli, Head of Clinical Microbiology, University Hospital Basel, and of the Applied Microbiology Research Group, Department of Biomedicine, University of Basel
Prof. Lubor Borsig, research group leader at the Institute of Physiology, University of Zürich
Prof. Luigi Terracciano, Head of Molecular Pathology, at the Institute of Pathology, University of Basel

Dernière mise à jour de cette présentation du projet 23.07.2020

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