Men and women often differ in cancer risk, progression, side effects, and survival. Now, new research shows that the microbes inside tumors differ between males and females and may help explain cancer outcomes.

The findings, published in Cell Reports Medicine, suggest that tumor microbes could in the future be used to better predict prognosis and personalize cancer therapy.

Some of the sex differences in cancer risk and progression are linked to hormones, metabolism, and lifestyle, but they are not fully understood. At the same time, scientists now know that tumors contain their own communities of microbes, which can affect how cancers grow, spread, and respond to drugs. 

Researchers led by Yuting Shan at the University of Minnesota in Minneapolis analyzed more than 5,000 tumor samples from five cancers to see whether microbes living inside tumors differ between men and women.

Sex differences

The total variety of microbes inside tumors did not differ much between men and women, but specific microbes did. Some were more common in male tumors, others in female tumors, and the pattern depended on cancer type. For example, certain fungi were more common in colorectal cancers from women, while Epstein-Barr virus was more common in stomach tumors from men. 

Many of the microbes identified have already been connected to cancer in previous studies. Some have been linked to poor drug response, while others have been associated with tumor growth or better treatment outcomes. 

The presence of certain microbes was associated with major shifts in tumor gene activity and the immune environment around the cancer. For example, female-associated microbes were linked to signaling pathways involved in hormones and immune defense, while male-associated microbes tended to show the opposite pattern. 

Cancer outcomes

People whose tumors contained Epstein-Barr virus tended to live longer than those without it. In lab experiments, stomach cancer cells containing the virus were more sensitive to several common chemotherapy drugs. 

The researchers also found that a bacterium called Capnocytophaga was more common in female head-and-neck tumors, and people with higher levels of this bacterium tended to survive longer. In lab tests, exposure to substances produced by the bacterium slowed cancer cell growth, and tumors with more Capnocytophaga showed signs of a more inflammatory environment, which may help explain the better survival seen in patients.

“Together, these findings reveal a sex-biased intratumoral microbiome axis that shapes tumor phenotypes and disease outcomes, highlighting opportunities for microbiota- guided, sex-aware approaches in oncology,” the authors say.