In a new study published in Cancer Cell titled, “Tumor-infiltrating bacteria disrupt cancer epithelial cell interactions and induce cell-cycle arrest,” researchers from the University of Texas MD Anderson Cancer Center have discovered a previously unknown mechanism that explains how bacteria can drive treatment resistance in patients with oral and colorectal cancer.
While tumor-infiltrating bacteria have been known to impact cancer progression and treatment, the mechanism has been unclear. Results demonstrate how the bacteria, Fusobacterium nucleatum (Fn), can induce a reversible state, known as quiescence, in cancer epithelial cells to allow tumors to evade the immune system and resist 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,” said Susan Bullman, PhD, associate professor of Immunology and associate member of MD Anderson’s James P. Allison Institute and corresponding author of the study. “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.”
According to the study, a bacterium can enter tumors and surround tumor epithelial cells, effectively cutting off their communication with surrounding cells to cause the cancer to enter a temporary resting state known as quiescence. This state allows cancer cells to evade the immune system, resist chemotherapy and promote metastasis.
Researchers discovered this ability when they observed that Fusobacterium is enriched in areas of the tumor with reduced epithelial cell density and decreased transcription activity. Preclinical models showed that Fusobacterium accumulates in specific parts of the tumor, settling between cancer cells, to interfere with them and make them less vulnerable to certain chemotherapies.
Spatial analysis validated these findings both in vivo and in a cohort of 52 patients with colorectal and oral cancer. In an independent patient cohort, higher levels of this bacterium were associated with lower expression of genes that allow for immune detection and with reduced treatment response.
The authors note that the study was limited by the experimental conditions, including laboratory bacterial doses and oxygen levels, which may not fully capture the complex tumor microenvironment.
At MD Anderson, Bullman and colleagues are uncovering how microbes influence treatment resistance and tumor progression in gastrointestinal cancers to build a foundation for new strategies to counteract microbial effects on cancer.
In parallel, their teams also are exploring ways to engineer tumor-targeting bacteria as a future therapeutic tool. This approach, sometimes called using “bugs as drugs,” offers a promising method to overcome the barriers posed by solid tumors, which often are resistant to traditional therapies.
