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RESEARCH AREA AND TRANSLATIONAL RESEARCH

The research activity of the LRS group focuses on the interaction between gut microbiota and immune system in gastrointestinal diseases, primarily colorectal cancer (CRC), or in systemic diseases of surgical relevance, such as obesity.

Starting from the analysis of the gut microbiota and the immune contexture in human samples, the LRS group aims at:

  • identifying novel biomarkers predictive of long-term response to surgical or medical treatment,
  • identifying patients at high risk of recurrence who may benefit of additional therapies,
  • developing novel therapeutic concepts based on gut microbiota conditioning through administration of selected probiotics or targeted antibiotics.

The gut microbiota consists of trillions of microorganisms critically shaping immune system development and immune responsiveness, through their effects on host metabolism.

In pathological conditions associated with increased gut permeability, such as cancer or inflammatory diseases, defined species of the gut microbiota translocate from the lumen into the lamina propria of the intestinal mucosa and therefore directly interact with epithelial cells and infiltrating immune cells.

Recent studies of the LSR group in CRC have demonstrated the capacity of bacterial components of the gut microbiota to induce, upon direct contact with tumor cells, expression of chemokines recruiting into the tumor bed immune cells predictive of favorable clinical outcome. Analysis of tumor-associated microbiota in human CRC samples has led to the identification of a group of bacteria positively associated with high immune cell infiltration and prolonged patients’ survival.  Immunomodulatory properties of identified bacteria and their capacity to promote antitumor effects are currently being investigated in in vitro and in vivo models.

On the other hand, defined bacterial species enriched in CRC tissues have been found to mediate pro-tumorigenic effects. In particular, Fusobacterium nucleatum, is associated with a poor response to chemotherapy and unfavorable prognosis.

In collaboration with the Oncology Department of EOC, a clinical study has recently been initiated, to evaluate the effectiveness of pre-operative antibiotic therapy with metronidazole to reduce tumor colonization by Fusobacterium nucleatum in patients with CRC undergoing surgery.

A more recent project related to obesity, aims at characterizing microbial species present in the visceral fat of obese patients and their potential association with long-lasting effectiveness of bariatric surgery.

In collaboration with the Infection Disease Unit and the Institute of Pharmacology of EOC, the LSR group has also evaluated the impact of the gut microbiota composition on immune responses to SARS-CoV-2 in COVID patients and in healthy subjects undergoing vaccination.

RESEARCH METHODS

The experimental approach of the LSR group combines ex-vivo analysis of human samples with in vitro and in vivo models.

Gut microbiome analysis is performed on freshly isolated archival tissues upon amplification and sequencing of 16S gene or, for fecal samples, shotgun metagenomics. The immune contexture is analyzed based on expression of large panels of immune cell-related genes, or, on freshly isolated samples, by large-scale flow cytometry.

Immunomodulatory properties of identified bacterial species are tested in in vitro and in vivo.

A platform for culture of bacterial species, including aerobic and anaerobic bacteria has been established within the LSR group, in collaboration with the group of Prof. Tonolla (SUPSI).

Expanded bacteria are cultured with human or murine immune cells, isolated through well-established protocols, and immune cell activation is evaluated based on expression of activation markers, proliferation, and release of cytokines and effector molecules.

Selected bacteria are evaluated in vivo, in orthotopic CRC mouse models, based on injection of tumor cells in the cecum or rectum wall. Developing tumors display bacterial colonization as well as immune cell infiltration and are therefore amenable to evaluate immunomodulatory and pro- or anti-tumor effects of bacterial species under investigation and of potential targeted antibiotic therapies.

GROUP LEADER
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Prof. Dr. med. Giandomenica Iezzi

BRIEF CV

Prof. Dr. med. Giandomenica Iezzi was trained at the University of Milan where she obtained a MD degree with full marks in 1994 and a specialization in Immunology and Clinical Allergology in 2001. During her training she has combined clinical activity  and research and since 2002 she has been fully dedicated to research. She has worked at the research center Department of Biotechnology (DIBIT) of the San Raffaele Hospital in Milan, the Basel Institute of Immunology, in Basel, of which she was a member from 1998 to 2000, the Federal Polytechnic of Zurich, from 2002 to 2007, and the Department of Biomedicine of the University of Basel, from 2007 to 2018.

In 2011 she obtained a “Professorship” from the Swiss National Fund which allowed her to establish an independent research group at the University of Basel.

Since 2019 she is responsible of the Translational Research Laboratory of the Department of Surgery of the Cantonal Hospital and since 2020 Titular Professor at the Faculty of Biomedical Sciences of the University of Italian Switzerland.

Her main research interest is represented by the interactions between the intestinal microbiota and the cells of the immune system in diseases of the gastrointestinal tract of surgical relevance, in particular colorectal  cancer.

Prof. Iezzi is author of> 60 original scientific publications in high impact journals and reviewer for major scientific journals and national and international funding agencies.

She is a member of the American Association for Cancer Research (AACR) and the Swiss Society of Allergology and Immunology (SSAI).

RESEARCHERS
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Camilla Basso

SENIOR POSTDOC

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Julija Djordjevic

PHD STUDENT

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Jacopo Galafassi

SURGEON IN TRAINING

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Elisa Sorrenti

PHD STUDENT

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Laura Terzaghi

RESEARCH ASSISTANT

RECENT PUBLICATIONS
  • Droeser RA, Iezzi G.  IL-22-mediates Cross-talk between Tumor Cells and Immune Cells Associated with Favorable Prognosis in Human Colorectal Cancer. J Cell Immunol. 2021;3:118-121.
  • Tosti N, Cremonesi E, Governa V, Basso C, Kancherla V, Coto-Llerena, Amicarella F, Weixler B, Däster S, Sconocchia G, MajnoPE, Christoforidis D, Tornillo L, Luigi Terracciano L, Ng CKY, Piscuoglio S, von Flüe M, Spagnoli, G, Eppenberger-Castori S, Iezzi G*, Droeser RA*. Infiltration by interleukin-22 producing T cells promotes neutrophil recruitment and predicts favorable clinical outcome in human colorectal cancer. Cancer Immunol Res, 2020, 8:1452-1462   * equal contribution
  • Arriga R, Caratelli S, Lanzilli G, Ottaviani A, Cenciarelli C, Sconocchia T, Spagnoli GC, Iezzi G, Roselli M, Lauro D, Coppola A, Dotti G, Ferrone S, Sconocchia G. CD16-158-valine chimeric receptor T cells overcome the resistance of KRAS-mutated colorectal carcinoma cells to cetuximab. Int J Cancer. 2020, 146:2531-2538.
  • Roviello G, D’Angelo A, Generali D, Pittacolo M, Ganzinelli M, Iezzi G, Manzini N, Sobhani N. Avelumab in gastric cancer. Immunotherapy. 2019 :759-768.
  • Manfredonia C, Muraro MG, Christian Hirt C, Valentina Mele V, Governa V, Adam Papadimitropoulos A, Däster S, Soysal SD, Droeser RA, Mechera R, Oertli D, Rosso R, Martin Bolli M, ZettlA, Terracciano LM, Spagnoli GC, Martin I*,and Iezzi G (* equal contribution). Maintenance of primary human colorectal cancer microenvironment using a perfusion bioreactor-based 3D culture system. Advanced Biosystems, 2019, 3: 1800300.
  • Governa V, Brittoli A, Mele V, Pinamonti M, Terracciano L, Muenst S, Iezzi G, Spagnoli GC, Zajac P, Trella E. A replication incompetent CD154/CD40L recombinant vaccinia virus induces direct and macrophage-mediated anti-tumor effects in vitro and in vivo. Oncoimmunology, 2019, 8:e1568162.
  • Iezzi G, Cremonesi E, Majno PE. Pro-tumoral role of gut bacteria: sabotaging immune cell recruitment. Annals of Translational Medicine, 2019, 7:59.
FUNDINGS
  • Swiss National Science Foundation
  • Swiss Cancer Research Foundation
  • Gebert Ruf Foundation
  • Area Formazione Ricerca Insegnamento EOC
  • Intramural funding of the Department of Surgery
  • Lega Ticinese contro il cancro
PHOTOGALLERY