Chronic psychological stress may promote tumor growth by helping cancers evade the body's immune defenses, according to researchers at Weill Cornell Medicine. The findings were published in the journal Cancer Cell.

The researchers uncovered a previously unknown chain of events linking chronic stress, the gut microbiome, and cancer progression. Experiments in mice and analyses of human tumor samples showed that prolonged stress disrupts the intestinal barrier, allowing certain gut bacteria to enter the bloodstream and eventually infiltrate tumor tissue.

Once inside the tumor, these bacteria release viruses that naturally infect them, known as bacteriophages. The viral DNA activates the TLR9 receptor in tumor-associated fibroblasts—cells that support tumor growth. In response, these fibroblasts begin producing large amounts of glucocorticoids, the body's primary stress hormones.

The local increase in glucocorticoids suppresses the activity of B lymphocytes, a key component of the anti-cancer immune response responsible for producing antibodies. As a result, the tumor gains additional protection from immune attack.

"Our findings open up many new avenues for research and create opportunities to develop new treatments and prognostic tests for cancer patients," said the study's senior author, Professor Melody Zeng.

The researchers also demonstrated that this mechanism can be interrupted. In mice, blocking the TLR9 receptor or eliminating bacteria directly within the tumor using antibiotics restored anti-tumor immune activity.

The team paid particular attention to Enterococcus gallinarum, the bacterium that most frequently migrated from the gut into tumors in laboratory animals. In human colorectal cancer samples, the researchers identified a different bacterium—Klebsiella pneumoniae—containing a high number of bacteriophages. Introducing this bacterium into mice significantly accelerated tumor growth. Analysis of brain tumor samples also revealed the presence of the gut bacterium Enterococcus faecium and its associated bacteriophages.

"I wouldn't be surprised if several species of gut bacteria are involved in this process, particularly those capable of adapting to life outside the intestine," Professor Zeng said.

According to the authors, the findings highlight the importance of managing chronic stress in patients with cancer. The researchers also plan to investigate whether detecting bacteriophages within tumors could serve as a prognostic biomarker and which therapeutic strategies targeting this pathway may prove most effective.