Periodic Reporting for period 4 - Tumor microbiome (The tumor microbial communities: Characterization, effects and translational opportunities)
Période du rapport: 2023-11-01 au 2024-04-30
In the current project, we suggested to greatly increase the characterization of the tumor microbiome, studying its effects on tumor biology, and capitalizing on the findings to introduce novel treatment modalities. We hypothesize that bacteria in tumors have a yet unknown influence on many aspects of tumor biology and that better characterization of these effects would thus lead to completely new treatment options.
We have done a few screens looking for the effect of bacteria on response to anti-cancer drugs and decided to follow an interesting finding in which bacteria that are present in lung cancer can reduce the sensitivity of lung cancer cells to commonly used anti-cancer treatment. We are now working on dissecting the molecular mechanism by which the bacteria mediate this effect.
We have also been using bacteria as a novel anti-cancer drug. We found that some bacteria home preferentially to tumors upon their intravenous (IV) injection. We thus use attenuated bacteria that we genetically engineer to deliver payloads to the tumor. We show that the presence of the bacteria in the tumors and the specific payloads that we add to them can activate the immune response and lead to tumor retraction in multiple mice cancer models.
We also explored the presence of fungi in tumors. In a comprehensive work that we published in 2022, we demonstrated that fungi can be found in almost all types of solid human tumors. We showed that tumor-type specific fungal signatures could be found and that the load and identity of the fungi in tumors may correlated to many clinical phenotypes, including overall survival. We were also found specific connections between bacteria, fungi, and immune cells in human tumors.
We have previously demonstrated that specific bacteria can be found in human pancreatic tumors and can degrade the anti-cancer drug gemcitabine and thus confer drug resistance. Now, using advanced technology, which allows us to grow human tumors in the lab, we are exploring how addition to antibiotics can synergize with gemcitabine. We have also started recently a clinical trial in which we test the effect of antibiotic treatment on the response of pancreatic cancer patients to gemcitabine.