Scientists have for long been concerned about why some people with liver cancer respond when given immunotherapy but others don’t. A recent comprehensive review provides key insights linking how patients respond to these treatments to the status of their gut microbiome.
The review, published in the journal Cancer Biology and Medicine, was conducted by a team based at the Chinese University of Hong Kong. The scientists compiled recent scientific data detailing how the microbial composition of the gut impacts how different patients respond when they are given immune checkpoint blockade therapies against hepatocellular carcinoma, the most common type of liver cancer.
They found that anti-tumor immune activity is modulated or influenced by several gut-linked factors like intratumoral microbes, bacteria in the gut and even the metabolites of the gut bacteria.
The data the researchers reviewed showed that under normal circumstances, immune balance is maintained via the presence of beneficial bacteria, such as Lactobacillus reuteri that produce microbial metabolites like butyrate and acetate that protect the liver and body from cancer proliferation.
However, when dysbiosis sets in, HCC (Hepatocellular carcinoma) develops after harmful microbes like klebsiella grow to excessive levels and produce metabolites that are toxic to the liver. These toxic metabolites trigger chronic inflammation, with the net result that tumor growth is enabled.
The review highlights the exact microbial signatures that are present in patients who are resistant to immunotherapy. For example, high levels of Phocaeicolavulgatus impair T-cell potency by lowering the available indole-3-acetic acid that these T-cells depend on to be effective in attacking tumor cells. These findings make a strong case that the gut microbiome is a major driver determining whether immunotherapy succeeds or fails.
The authors say microbial populations that dominate the gut-liver axis can either make the tumor cold (unresponsive to immune system attack) or warm (vulnerable to being successfully attacked by the immune system).
The study has several clinical implications in the treatment of HCC. First, profiling the gut microbiome can help in determining which patients are likely to benefit from immunotherapy and which ones are unlikely to respond. Secondly, interventions targeting the gut microbiome can be administered to boost the immune system’s ability to attack the liver cancer.
Some possible interventions included in the review are dietary fiber supplementation to ramp up the production of short-chain fatty acids linked to healthy immune system function, transplanting fecal microbiota into patients whose microbiome is out of balance and therefore unsupportive to the immune system’s cancer fight, and several other interventions currently being clinically tested to restore gut microbiome balance so that cancer proliferation is suppressed.
As more is understood about the different ways in which the gut microbiome can be supported to make checkpoint-inhibitors or blockades more effective, the treatments being developed by several firms like Calidi Biotherapeutics Inc. (NYSE American: CLDI) could be supercharged to benefit more patients.
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