A breakthrough study from MD Anderson Cancer Center demonstrates how bacteria inside tumors make certain cancers resistant to treatment, potentially changing future therapeutic approaches.
Researchers at The University of Texas MD Anderson Cancer Center have uncovered a vital, previously unknown mechanism whereby bacteria contribute to treatment resistance in patients with oral and colorectal cancer.
Published in the journal Cancer Cell, this study may pave the way for more effective cancer treatments.
Researchers have long known that tumor-infiltrating bacteria can affect cancer progression and treatment outcomes. However, the exact mechanisms behind this influence were largely unclear.
This new study sheds light on how certain bacteria, particularly Fusobacterium nucleatum (Fn), can induce a state of quiescence in cancer epithelial cells. This reversible resting state allows tumors to evade the immune system and resist the effects of chemotherapy.
“These bacteria-tumor interactions have been hiding in plain sight, and with new technologies we can now see how microbes directly affect cancer cells, shape tumor behavior and blunt the effects of treatment,” corresponding author Susan Bullman, an associate professor of immunology and associate member of MD Anderson’s James P. Allison Institute, said in a news release. “It’s a whole layer of tumor biology we’ve been missing and one we can now start to target. We hope these findings help open the door to designing smarter, microbe-aware therapies that could make even the toughest cancers more treatable.”
Understanding the Mechanism
During their investigation, the researchers discovered that Fusobacterium can infiltrate tumors and surround epithelial cells, effectively severing their communication with surrounding cells and inducing quiescence.
This state not only allows cancer cells to evade immune detection but also makes them resilient against chemotherapy and promotes metastasis.
The team first observed that Fusobacterium levels were higher in areas of tumors with reduced epithelial density and lower transcription activity. Using preclinical models, they demonstrated that Fusobacterium accumulates in specific tumor regions, settling between cancer cells, and decreasing their vulnerability to chemotherapy.
Spatial analysis in both live models and a cohort of 52 colorectal and oral cancer patients confirmed these findings. An independent patient cohort showed that higher levels of this bacterium were linked to lower gene expression for immune detection and a reduced response to treatment.
Significance and Future Directions
Understanding how microbes like Fusobacterium influence cancer treatment resistance is crucial for developing new therapeutic approaches.
The researchers are also exploring innovative strategies like engineering tumor-targeting bacteria, a concept known as “bugs as drugs,” which might offer new ways to tackle solid tumors resistant to traditional therapies.
While this study provides significant insights, it is not without limitations. The experimental conditions, including laboratory bacterial doses and oxygen levels, may not fully replicate the complex environment of human tumors. Further research is necessary to deepen our understanding of these interactions in vivo.