Translational Research in Immuno-oncology and Microbiome (TRIM)

Our Reserach

Immunofluorescence microscopy of a small intestine (ileum). Nuclei: blue, CD3: green, PanCK: Pink. The picture shows a transversal cut of ileum tissue, with typical finger-like projections (villi). At the top and bottom, Peyer Patches (aggregated lymphoid follicles, in green) can be observed.

Immunotherapy led to a paradigm change of systemic tumor therapy. Many patients now benefit from improved survival and sometimes cure. However, there is urgent need to further improve immunotherapy, as a majority of patients will progress despite treatment. Recent preclinical translational and clinical studies demonstrate that the patient's (gut) microbiome is a major determinant of response to immunotherapy and highlight the potential of microbiome intervention in immuno-oncology.

In our team, we actively integrate translational data, functional assays and preclinical models, to understand and overcome mechanisms of resistance to immunotherapy and chemotherapy, with a focus in gut-related subversion of anti-tumor immunity. By leveraging this knowledge, we aim to find biomarkers, patient stratification and innovative treatment combinations.

Our research group, is embedded in a multidisciplinary team with close connection to the clinic and a bioinformatics team.

Future outlook: We will continue our efforts to improve the understanding of tumor-microbiome-host interactions with a focus on T cell- and tumor-intrinsic mechanisms of resistance in Immuno-Oncology. Our ultimate goal is to bring microbiome-based personalized I-O to patients.

Projects

Mucosome

To bring Fecal Microbiota Transfer (FMT) therapy to the standard of care, the open challenge is to identify cancer patients at risk of gut-related therapy failure who are amenable to FMT. We are currently collaborating with clinicians and scientists at UKHD and NCT (Dr. C. Rauber) to conduct the "Mucosome" study (S-633/2021) with the aim of identifying biomarkers in patients with extraintestinal cancers that can be used for the selection of patients who will potentially benefit from FMT and to identify stool donors that can be used pharmacologically in a tailored donor-recipient approach in cancer therapy.

DFG Individual Research Grant. Project no. 537739196. (2024-2027)

Team

Dr. Maria Paula Roberti

Group head
Dr. Andrea Leufgen

Postdoctoral researcher
Jasmin Zech

PhD candidate
Annika Steitz

MD candidate
Güner Can

MD candidate (with AG Rauber, UKHD)
Claudia Luckner-Minden

Technical assistant

Entire Team

Selected Publications

2023 - Science

A microbiota-modulated checkpoint directs immunosuppressive intestinal T cells into cancers.

Fidelle M, Rauber C, Alves Costa Silva C, Tian AL, Lahmar I, de La Varende AM, Zhao L, Thelemaque C, Lebhar I, Messaoudene M, Pizzato E, Birebent R, Mbogning Fonkou MD, Zoppi S, Reni A, Dalban C, Leduc M, Ferrere G, Durand S, Ly P, Silvin A, Mulder K, Dutertre CA, Ginhoux F, Yonekura S, Roberti MP, Tidjani-Alou M, Terrisse S, Chen J, Kepp O, Schippers A, Wagner N, Suárez-Gosálvez J, Kobold S, Fahrner JE, Richard C, Bosq J, Lordello L, Vitali G, Galleron N, Quinquis B, Le Chatelier E, Blanchard L, Girard JP, Jarry A, Gervois N, Godefroy E, Labarrière N, Koschny R, Daillère R, Besse B, Truntzer C, Ghiringhelli F, Coatnoan N, Mhanna V, Klatzmann D, Drubay D, Albiges L, Thomas AM, Segata N, Danlos FX, Marabelle A, Routy B, Derosa L, Kroemer G, Zitvogel L. A

2020 - Nature Medicine

Chemotherapy-induced ileal crypt apoptosis and the ileal microbiome shape immunosurveillance and prognosis of proximal colon cancer.

Roberti MP, Yonekura S, Duong CPM, Picard M, Ferrere G, Tidjani Alou M, Rauber C, Iebba V, Lehmann CHK, Amon L, Dudziak D, Derosa L, Routy B, Flament C, Richard C, Daillère R, Fluckiger A, Van Seuningen I, Chamaillard M, Vincent A, Kourula S, Opolon P, Ly P, Pizzato E, Becharef S, Paillet J, Klein C, Marliot F, Pietrantonio F, Benoist S, Scoazec JY, Dartigues P, Hollebecque A, Malka D, Pagès F, Galon J, Gomperts Boneca I, Lepage P, Ryffel B, Raoult D, Eggermont A, Vanden Berghe T, Ghiringhelli F, Vandenabeele P, Kroemer G, Zitvogel L.

2019 - Cell Research

Sustained Type I interferon signaling as a mechanism of resistance to PD-1 blockade.

Jacquelot N, Yamazaki T, Roberti MP, Duong CPM, Andrews MC, Verlingue L, Ferrere G, Becharef S, Vétizou M, Daillère R, Messaoudene M, Enot DP, Stoll G, Ugel S, Marigo I, Foong Ngiow S, Marabelle A, Prevost-Blondel A, Gaudreau PO, Gopalakrishnan V, Eggermont AM, Opolon P, Klein C, Madonna G, Ascierto PA, Sucker A, Schadendorf D, Smyth MJ, Soria JC, Kroemer G, Bronte V, Wargo J, Zitvogel L.

2018 - Science

Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors.

Routy B, Le Chatelier E, Derosa L, Duong CPM, Alou MT, Daillère R, Fluckiger A, Messaoudene M, Rauber C, Roberti MP, Fidelle M, Flament C, Poirier-Colame V, Opolon P, Klein C, Iribarren K, Mondragón L, Jacquelot N, Qu B, Ferrere G, Clémenson C, Mezquita L, Masip JR, Naltet C, Brosseau S, Kaderbhai C, Richard C, Rizvi H, Levenez F, Galleron N, Quinquis B, Pons N, Ryffel B, Minard-Colin V, Gonin P, Soria JC, Deutsch E, Loriot Y, Ghiringhelli F, Zalcman G, Goldwasser F, Escudier B, Hellmann MD, Eggermont A, Raoult D, Albiges L, Kroemer G, Zitvogel L.

Full list of publications

Link to all publications