Microbiome
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.
Project: 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 gut 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.
Project: FLORA trial
In multifocal hepatocellular carcinoma, the recently introduced first-line therapy Atezolizumab/Bevacizumab leads to an objective response rate of only 27%, which is superior to previous first-line therapies but highlights the urgent need for further therapeutic improvement. Together with Dr. C. Rauber (UKHD) and Dr. M. Dill (UKHD/DKFZ), who conduct "The FLORA trial: Fecal Microbiota Transfer in Liver Cancer to Overcome Resistance to Atezolizumab/Bevacizumab" Dr. M. Paula Roberti and the CCU team will perform the accompanying translational research program. Part of the "NCT Proof-of-Concept Trial Program" within the framework of Liver Cancer Center Heidelberg (LCCH), FLORA is a randomized, single-blind, placebo-controlled phase II clinical trial, which aims to assess immunogenicity and safety of FMT in combination with standard of care immunotherapy in advanced hepatocellular carcinoma.
Contact
Maria Paula Roberti, PhD - mariapaula.roberti@nct-heidelberg.de
Publications
Roberti MP, (...) Zitzvogel L.Chemotherapy-induced ileal crypt apoptosis and the ileal microbiome shape immunosurveillance and prognosis of proximal colon cancer. Nat Med. 26(6):919-931 (2020). doi: 10.1038/s41591-020-0882-8.
Picard M, (...) Roberti MP. Ileal immune tonus is a prognosis marker of proximal colon cancer in mice and patients. Cell Death Differ. 28(5):1532-1547 (2021). doi: 10.1038/s41418-020-00684-w.
Jacquelot N*, Yamazaki T*, Roberti MP*, (...) Zitvogel L. Sustained Type I interferon signaling as a mechanism of resistance to PD-1 blockade. Cell Res. 29(10):846-861 (2019). doi: 10.1038/s41422-019-0224-x. *Co-shared first authors.
Routy B, Le Chatelier E, Derosa L, Duong CPM, Alou MT, Daillère R, Fluckiger A, Messaoudene M, Rauber C, Roberti MP, (...) Zitvogel L. Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors. Science. 359(6371):91-97 (2018). doi: 10.1126/science.aan3706.
Pitt JM, Vétizou M, Daillère R, Roberti MP, (...) Zitvogel L. Resistance Mechanisms to Immune-Checkpoint Blockade in Cancer: Tumor-Intrinsic and -Extrinsic Factors. Immunity. 44(6):1255-69 (2016). doi: 10.1016/j.immuni.2016.06.001.