Microbes within metastatic cancer tumors could affect the success of immunotherapy, a study has found, with one bacterium in particular implicated in poor outcomes.
The research in more than 4000 tumor tissue samples, involving 26 types of cancer, could guide the development of bacteria-oriented strategies to enhance cancer therapy.
The type of bacteria present was closely related to location of the metastatic tumor, the conditions there, and the type of cancer.
The investigators note in the journal Cell that fusobacterium was linked with a poor response to immune checkpoint blockade in lung cancer.
“Our work opens doors for exploring new forms of treatments, for example against bacteria that might help the tumor,” said researcher Iris Mimpen, a PhD student at the Netherlands Cancer Institute.
“It helps us understand how the complex environment of tumors works, an environment in which all kinds of cells—including bacteria—live together and influence each other.”
Microbial communities in primary tumors have previously been found to be distinct from those in non-malignant tissue and can reprogram the tumor microenvironment.
However, the biological and clinical relevance of the microbiome in metastases is unclear, despite these tumors being responsible for most solid cancer deaths and key targets for systemic anti-cancer therapies.
To investigate further, the researchers integrated metagenomics, genomics, and transcriptomics to profile biopsy microbiomes from 4,160 metastatic tumors.
They further examined the persistence of the microbiome over time and under therapeutic pressure in a separate group of 185 paired biopsies of metastatic cancers.
The results revealed that the metastatic microbiome was dominated by anerobic bacteria and influenced by the anatomical site.
It could also be reshaped after immunotherapy treatment and could predict the efficacy of immune checkpoint blockade.
Immunotherapy augmented the metastatic tumor microbiome and reduced bacterial diversity, which was even more pronounced in patients who were responsive to treatment.
Fusobacterium was negatively associated with responsiveness to immune checkpoint blockade in non-small cell lung cancer, the authors note.
This gram-negative anerobic oral commensal can directly interact with tumor-infiltrating lymphocytes to suppress their activities and may also indirectly contribute to immunosuppression through the secretion of bacterial-derived metabolites or outer membrane vesicles.
The team concludes: “We expect that our data will serve as an important community resource to enable future studies on the complex, potentially targetable roles of the intratumor microbiome in metastatic cancers.”
