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inhibitors Checkpoint, designed to unleash the power of the immune system on tumors are some of the most impressive new treatments against cancer. But most patients who receive no benefit. Two new mouse studies suggest a surprising reason why these people may not have the right mix of bacteria in their guts. Both studies show that the composition of the gut microbiome-the living microorganisms swarms naturally in the intestines determines the effectiveness of cancer immunotherapies are.
The studies are the first to connect our intestinal inhabitants the power of checkpoint inhibitors, drugs which counteract one of the tricks of survival of cancer. To curb the attacks on our own tissues, immune cells carry receptors that connect to their business. However, tumor cells can also stimulate these receptors, preventing the immune system from attacking them. Checkpoint inhibitors as ipilimumab, which has been on the market since 2011-nivolumab pembrolizumab and prevent tumor cells to stimulate the receptors.
The new work could change the way doctors use drugs. "The two papers convincingly show that microbes can affect treatment," says immunologist Yasmine Belkaid of the National Institute of Allergy and Infectious Diseases in Bethesda, Maryland, who was not connected to the new studies. In past, researchers have generally sought mutations in the genomes of patients that could explain why a particular checkpoint inhibitor does not work, says molecular biologist Scott Bultmann of the University of North Carolina School of Medicine in Chapel Hill. the new results are encouraging, he says, because "it is easier to change your intestinal microbiota of your genome."
Checkpoint inhibitors may shrink tumors and extend patients' lives, sometimes by years. Yet only a fraction of the beneficiaries to improve. Approximately 20% of melanoma patients treated with ipilimumab live longer, for example. Researchers do not know what distinguishes them from the other 80%.
A side effect oncoimmunologist Laurence Zitvogel direction of drug Cancer Campus Gustave Roussy in Villejuif, France, and colleagues to the microbiome. The ipilimumab often triggers colitis, an inflammation of the large intestine, where some of our microbiome lives. This side effect suggests checkpoint inhibitors and interaction between the microbiome. Following this possibility, the researchers tracked the growth of tumors implanted in mice without intestinal bacteria. Inhibitory control point, they tested was less powerful animals.
Further analysis by Zitvogel and colleagues suggested that some bacteria in Bacteroides and Burkholderia genres were responsible for the antitumor effect of the microbiome. To confirm this possibility, the researchers transferred the microbes in mice that lacked the intestinal bacteria or feeding animals microorganisms or by giving them Bacteroides rich excrement of certain treaties ipilimumab patients. In either case, an influx of microbes reinforced the response of animals to a checkpoint inhibitor. "Our immune system can be mobilized by the trillions of bacteria in our gut," says Zitvogel.
immunologist Thomas Gajewski of the University of Chicago (UC) in Illinois and colleagues came to the same conclusion after noticing a disparity between the mice they had obtained from two suppliers. melanoma tumors grew more slowly in laboratory mice that Jackson mice Taconic Farms. the microbiomes rodents tend companions cage-homogenize the animals eat feces to the other, the researchers housed mice of both suppliers together. Cohabitation erased the difference in tumor growth, indicating that it depends on the types of microbes in the guts of rodents .
When they analyzed the microbiomes mice, researchers have identified a bacterial genus known Bifidobacterium . The team found that feeding mice from Taconic Farms a probiotic that contains several Bifidobacterium species have increased the effectiveness of a checkpoint inhibitor against tumors. "The endogenous antitumor response is greatly influenced by your commensal bacteria," says co-author Ayelet Sivan, who was a Ph.D. student at UC when the research was conducted. Both groups reported their findings online today in Science .
The two teams involved different bacterial groups, but that does not worry microimmunologist Christian Jobin of Florida College of Medicine University Gainesville. "Different medications, different bugs, but the same criteria," he said. He added that the new work complements a pair of 2013 studies which demonstrated that the microbiome affects how chemotherapy works.
The discovery "opens up new ways to potentially increase the therapy," says Cynthia Sears, an infectious disease specialist at Johns Hopkins School of Medicine in Baltimore, Maryland. For example, it may be possible enhance the antitumor response of a patient with probiotics. But researchers also see potential obstacles. as noted Zitvogel, regulators in the US and Europe have not approved the use of probiotics for patients cancerous. Also clear is how microbes stimulate immune response-intestinal bacteria are essential for the development of the immune system, but researchers are not sure how they twist its function in adult animals. And scientists are learning how to tinker with the microbiome. "clearly we can meaningfully manipulate the microbiota and create positive health effects," says Sears. However, the researchers say, studies suggest that we can have new powerful allies in the fight against cancer.
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