Researchers discovered how the gut microbiome helps our immune system fight tumors that are cancerous.
The gut microbiome has beneficial effects on health, and alterations in the microbiota can increase the risk of a number of illnesses. Past studies suggest that the gut microbiota can affect anti-tumor immunity, and recently, that it can be used to simulate the efficacy of immune checkpoint inhibitor therapy. Immune checkpoints are proteins that prevent immune cells from targeting and killing the body’s own cells. However, tumor cells can use these checkpoint proteins (CTLA-4, PD-1, or PD-L1) to evade the immune system’s attack.
Immune checkpoint inhibitors were developed to overcome tumor cells’ use of checkpoint proteins and have shown promise for a number of cancers. However, some cancer types are resistant to checkpoint inhibitor immunotherapy, and some patients do not respond well despite having cancers vulnerable to this treatment. Researchers from the Cumming School of Medicine, University of Calgary, studied the efficacy of checkpoint inhibitor immunotherapy in mouse models of colorectal and bladder cancer, and melanoma. They then studied if the effectiveness of the therapy depended on the gut microbiota.
Germ-free mice were colonized with one of 5 different species of gut microbiota. The monocolonized and non-colonized (germ-free) mice were injected with tumor cells. When tumors developed, all mice were treated with a checkpoint inhibitor. The results showed that 3 of the five bacterial species tested (Bifidobacterium pseudolongum, Lactobacillus johnsonii, and Olsenella) significantly increased the checkpoint’s efficacy inhibitor treatment compared to germ-free mice or mice monocolonized with the other two species (Colidextribacter or Prevotella species).
Serum metabolomics studies showed increases in the levels of several metabolites in the mice colonized with the three identified species, with the most abundant being inosine. Results of other published studies demonstrate that inosine supplementation enhances the anti-tumor efficacy of immune-checkpoint blockade. Taken together, specific intestinal bacteria increased the efficacy of immunotherapy response via a mechanism involving the production of inosine that is translocated systemically to activate T cells. Combination immunotherapy and treatment with critical gut bacteria can enhance immune checkpoint inhibitor immunotherapy.
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Researchers discover the microbiome's role in attacking cancerous tumors. (2020). Retrieved 9 September 2020, from https://www.sciencedaily.com/releases/2020/08/200813144920.htm