Continuing the dive into the impact of the human microbiome on the development of non-gastro-intestinal diseases and to follow up on last week's post by Adèle Richmond - two studies published last week found a link between the presence of certain intestinal bacteria with immunotherapy efficacy. The first study, conducted in mice models, not only found that mice with inadequate microbiomes (through broad spectrum antibiotics) fare significantly worse than their counterparts, but more importantly that supplementation through fecal transplant into these mice reversed and restored the PD-L1 inhibitor's efficacy, allowing the T lymphocytes to respond to the tumors appropriately. While the second study was a retrospective observational study in patients, in light of these animal models it raises interesting questions.
Though it's important to note that these studies are specific to anti-PD-1 immunotherapy in melanoma, and do not have any conclusions about chemotherapy or radiation therapy, this opens a wide door for the future of cancer treatment. Furthermore, it brings the role of antibiotics into question for cancer patients, similar to the the role of repeated antibiotic use in the development of Alzheimers Disease previously discussed. As antibiotics can wipe out gut bacteria and many cancer treatments induce immunosupression, what is the compatibility of these treatments with each other? Many recent findings have been pointing to how critical a healthy microbiome is to human health.
Some intestinal-dwelling bacteria appear to corral and train immune cells to fight off cancer cells—prior to any spurring from cancer immunotherapies. Without such microbial priming, the drugs may only offer a futile prod. In both studies, published this week in Science, researchers found that the cancer patients who saw no benefit from the drugs (non-responders) were the ones who lacked certain beneficial gut bugs, particularly after taking antibiotics. Meanwhile, cancer patients who did respond to the drugs had bacteria that could prompt the immune system to release chemicals that get cancer-killing immune cells—T cells—to chomp at the bit.