During the project, we were able to characterize the bacteria that reside in human tumors in an unprecedented way. We explored a cohort of more than 1,500 human tumors originating from eight different solid tumor types. We showed that bacteria can be found in all of these tumor types and that each tumor type has a different signature of bacteria. We found that most of the bacteria in tumors are intra-cellular, mostly in cancer and immune cells, and also found some bacteria that are correlated with response to immunotherapy. We also explored the functions of bacteria in specific tumor types, looking for their correlations with clinical phenotypes. For example, we showed that in lung tumors from smokers, there is an enrichment for bacteria that can degrade nicotine as compared to lung tumors from non-smokers. We could also culture live bacteria from human tumors and are now studying these bacteria and their effects in mice cancer models.
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.
