In a new study from the University of Toronto, researchers found how probiotic bacteria in the gut could undermine immunity in pancreatic cancer, pointing toward more personalized cancer treatments.
Lactobacillus—a type of bacteria thought to promote gut health—can alter the function of immune cells called macrophages in the pancreatic tumor environment and spur cancer growth.
Most studies focus on positive links between the microbiome and cancer outcomes.
This work focused on negative correlations of the microbiome with cancer, and suggests that in some conditions, the constituency of the microbiome may have a negative impact.
Macrophages are tissue-resident immune cells thought to play an important role in tumor growth and metastasis.
The researchers showed that Lactobacillus affects macrophage function by metabolizing dietary tryptophan, an essential amino acid found in protein from plant- and animal-based foods.
Deletion or inhibition of the aryl hydrocarbon receptor AHR in macrophages led to reduced growth of pancreatic cancer, better sensitivity to treatments and increased numbers of inflammatory T cells, the researchers found.
They then looked to Lactobacillus in part because previous studies had shown that the bacteria correlated with AHR activity and reduced inflammation, both of which can enable cancer growth.
They tested the effects of the bacteria in mice with surgical models of pancreatic cancer.
They also moved the project forward with single cell analysis—a technology that provides genome-scale data on individual cells.
The researchers later used tissue samples and data from human trials to show that high expression of AHR correlates with disease progression, immune suppression and patient survival.
Pancreatic cancer is notoriously difficult to treat.
Despite being relatively rare, and patients with the disease have not seen the gains in survival common in other cancers over the last three decades.
The team’s future work will collect stool samples before and after chemotherapy to look for enrichment of Lactobacillus, and whether the bacteria correlates to treatment response, patient survival and their observations on how it acts in the tumor environment.
The study was published in Immunity and was conducted by Tracy L. McGaha et al.
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