A study led by Weill Cornell Medicine investigators, published on June 25, 2026, in the journal Cancer Cell, found that chronic psychological stress helps tumors evade immune attack. This process occurs through a series of molecular events involving gut bacteria and viruses within these bacteria.

The research, conducted in mouse models under chronic unpredictable mild stress, revealed that the anti-tumor B cell response is suppressed. Researchers discovered that chronic stress causes some gut bacteria to escape from the gut and migrate to existing tumors. Viruses within these migrating bacteria induce cancer-associated fibroblasts (CAFs) inside the tumors to produce elevated levels of stress hormones, which then suppress local antitumor immunity.

Further investigation showed that chronic stress triggers the adrenal glands to produce stress hormones, increasing glucocorticoid levels in the gut. These high glucocorticoid levels activate receptors on gut-lining cells, weakening the gut lining. This weakened barrier allows specific gut bacteria to escape into the bloodstream and other tissues, including tumors.

In the mouse models used for the study, the bacterial species Enterococcus gallinarum was observed to dominate this gut-to-tumor microbial migration. Small viruses, known as phages, often emerge from E. gallinarum within tumors. The DNA from these phages then activates the DNA-sensing receptor TLR9 on the CAFs. This TLR9 activation prompts the fibroblasts to produce stress hormones, which subsequently suppress the immune system's antibody-making B cells.

Evidence of this mechanism was also found in samples of human colorectal tumors. A phage-laden gut bacterium, Klebsiella pneumoniae, isolated from human colon tumors, accelerated tumor growth in mice. An analysis of microbial genomic data from human brain tumor samples further suggested the presence of the gut-dwelling bacterium Enterococcus faecium and associated phages.

The researchers were able to prevent this immune-suppressing cascade in mouse models using a compound that blocks TLR9 signaling. They also achieved this by injecting an antibiotic into tumors to eliminate tumor-resident bacteria. Dr. Melody Zeng, associate professor of immunology in pediatrics and the study's senior author, commented on the broad applicability of the findings. "Our findings open up many new research directions, with possibilities for new treatments and prognostic tests for cancer patients," Zeng said. She added, "I wouldn't be surprised to see multiple gut bacterial species involved in this process, particularly the species that are more adaptable to tissue environments outside the gut."

Dr. Hilal Bashir, a postdoctoral associate in the Zeng Lab and the study's first author, stated, "These findings also underscore the importance of stress management in cancer and raise questions about existing therapeutic approaches that sometimes involve giving patients glucocorticoids." Dr. Zeng's team is currently investigating which therapeutic approach might be most effective against this process and whether detecting phages in tumors could have prognostic value.