• Researchers uncovered a previously unknown way for microbes within tumours to contribute to treatment resistance in certain cancers 

• Study finds these microbes push cancer cells into a reversible resting state, allowing them to become resistant to certain chemotherapies 

• Scientists hope understanding the microbe-tumour relationship will enhance future cancer treatment 

Researchers have discovered a previously unknown mechanism that explains how bacteria can drive treatment resistance in patients with oral and colorectal cancer. The study was published in Cancer Cell.

Tumour-infiltrating bacteria have been known to impact cancer progression and treatment, but very little is understood about how they do this.

The new study shows how certain bacteria – particularly Fusobacterium nucleatum (Fn) – can induce a reversible state, known as quiescence, in cancer epithelial cells.

This allows tumours to evade the immune system and resist chemotherapy.

“These bacteria-tumour interactions have been hiding in plain sight, and with new technologies we can now see how microbes directly affect cancer cells, shape tumour behaviour and blunt the effects of treatment,” said corresponding author Susan Bullman, Ph.D., associate professor of Immunology and associate member of MD Anderson’s James P. Allison Institute.

“It’s a whole layer of tumour 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.”

How do bacteria help cancer cells evade detection?

The study describes how a bacterium can enter tumours and surround tumour epithelial cells, effectively cutting off their communication with surrounding cells and causing the cancer cells to enter a temporary resting state known as quiescence.

This, in turn, allows them to evade the immune system, resist chemotherapy and promote metastasis.

Researchers discovered this ability when they first noticed that Fusobacterium is enriched in areas of the tumour with reduced epithelial cell density and decreased transcription activity.

Preclinical models showed that Fusobacterium accumulates in specific parts of the tumour, settling between cancer cells, interfering with them, and making 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.

Why is it important to understand the relationship between microbes and cancer?

At MD Anderson, the Bullman and Johnston labs are uncovering how microbes like Fn influence treatment resistance and tumour progression in gastrointestinal cancers.

This lays the groundwork for new strategies to counteract microbial effects on cancer.

In parallel, their teams also are exploring ways to engineer tumour-targeting bacteria as a future therapeutic tool.

This approach, sometimes called using “bugs as drugs”, offers a promising way to overcome the barriers posed by solid tumours, which often are resistant to traditional therapies.

What are the limitations of this study?

The study was limited by the fact that the experimental conditions, including laboratory bacterial doses and oxygen levels, may not fully capture the complex and dynamic environment within human tumours.

This highlights the need for further research to better understand these interactions in vivo.

Article: Tumor-infiltrating bacteria disrupt cancer epithelial cell interactions and induce cell-cycle arrest

Source: University of Texas M. D. Anderson Cancer Center