{"id":27407,"date":"2021-09-02T12:00:00","date_gmt":"2021-09-02T12:00:00","guid":{"rendered":"https:\/\/www.cancer.gov\/news-events\/cancer-currents-blog\/2021\/cancer-fungi-gut-radiation-therapy"},"modified":"2024-11-03T15:14:30","modified_gmt":"2024-11-03T15:14:30","slug":"gut-microbes-may-influence-how-well-radiation-therapy-works-against-cancer","status":"publish","type":"post","link":"https:\/\/ogkologos.com\/en\/gut-microbes-may-influence-how-well-radiation-therapy-works-against-cancer\/","title":{"rendered":"Gut Microbes May Influence How Well Radiation Therapy Works against Cancer"},"content":{"rendered":"

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Fungi in the gut (purple) may affect how tumors respond after radiation therapy by disrupting the immune system’s response to the cancer.<\/p>\n

Credit: Centers for Disease Control and Prevention\/Stephanie Rossow<\/p>\n<\/div>\n<\/figcaption><\/figure>\n<\/div>\n

Many studies have shown that bacterial communities in the gut may influence cancer in humans, from how fast tumors grow and spread to how they respond to treatments like chemotherapy or immunotherapy.<\/p>\n

But new research suggests that bacteria<\/a> aren\u2019t the only microorganisms<\/a> in the gut that affect how tumors respond to cancer treatments. Fungi<\/a>, the study found, may also be important players.<\/p>\n

In studies in mice, scientists from Cedars-Sinai Medical Center found that, when normal bacterial communities in the gut were disrupted, fungi moved in. And these fungi, in turn, disrupted the immune response to tumors<\/a> that may be important for radiation therapy<\/a> to work most effectively, the team reported in Cancer Cell<\/em> on July 29.<\/p>\n

The researchers also identified a fungi-sensing protein<\/a> in tumors that may play a role in this phenomenon. Using samples from human tumors, they found that people with breast cancer or melanoma<\/a> that had higher levels of this protein did not live as long as those who had lower levels.<\/p>\n

\u201cWe\u2019re just [beginning] to understand how the microbiota help in terms of host immunity in cancer therapeutics,\u201d said Mansoor Ahmed, Ph.D., of NCI\u2019s Division of Cancer Treatment and Diagnosis<\/a>, who was not involved with the study. A more detailed picture of these interactions could eventually help researchers design personalized treatments to alter the gut microbiome<\/a> prior to cancer therapy, Dr. Ahmed explained.<\/p>\n

Complex Interactions<\/h2>\n

The details of how the immune system<\/a> helps fight cancer are still being uncovered. Early work in the field led to the rise of immunotherapies<\/a>: cancer treatments that coax the immune system to attack and kill tumor cells. These therapies have already revolutionized the treatment of several types of advanced cancer<\/a>, including melanoma and lung cancer<\/a>.<\/p>\n

But recent research has revealed that the immune system can also influence how well chemotherapy and radiation therapy work. And research has shown that the microorganisms normally found in the human gut\u2014known as the gut microbiome\u2014affect how immune cells do their job throughout the body<\/a>.<\/p>\n

The new study, led by Stephen Shiao, M.D., Ph.D., and David Underhill, Ph.D., both of Cedars-Sinai Medical Center, sought to build on this earlier research.<\/p>\n

The role of the immune system in controlling cancer after radiation therapy has been under intensive study, Dr. Underhill explained. Without the contribution of immune cells, cancer cells are likely to grow back right after treatment. <\/p>\n

\u201cRadiation therapy kills tumor cells, then immune cells infiltrate [the tumor] and make it an inhospitable environment for the tumor cells to grow back,” he said. “It\u2019s like a forest fire, where you can put it out, but there has to be a team to go in and clean up all the hotspots and make sure they don\u2019t flare up and start all over again.\u201d<\/p>\n

\u201cSo why does a strong immune response happen sometimes [in tumors after radiation therapy] and not other times?\u201d Dr. Underhill asked. To investigate, the researchers looked more closely at the complex interactions between the microbiome and the immune system.<\/p>\n

Microbes Out, Microbes In<\/h2>\n

The researchers first used a cocktail of antibiotics to disrupt the normal gut bacterial communities in mice that had been implanted with breast cancer cells. When they treated the mice with radiation, the tumors continued to grow and the mice died quickly. The same thing happened in mice implanted with melanoma cells and in mice treated with a different combination of antibiotics.<\/p>\n

The researchers also noticed something else in the mice: The gut bacteria that had been wiped out by antibiotics were replaced by fungi. To see what role this overgrowth of fungi might be playing in the response of immune cells after radiation therapy, the team treated another group of mice with an antifungal drug before radiation.<\/p>\n

The antifungal treatment had the opposite effect from the antibacterial treatment: more tumor cells died after radiation therapy. <\/p>\n

Further experiments found that administering a large amount of fungi into the gut reduced the effectiveness of radiation therapy even if bacteria weren\u2019t depleted beforehand. This suggested that it was the presence of extra fungi\u2014not the reduction in bacteria\u2014that impaired the response to radiation therapy, the researchers reported.<\/p>\n

After depleting bacteria in the gut with antibiotics and letting fungi expand, the researchers also found fewer tumor cell\u2013killing immune cells in the tumor microenvironment<\/a> after the mice received radiation therapy. But when the gut fungi were kept in check with an antifungal drug, a larger number of these helpful immune cells reached the tumors after radiation therapy.<\/p>\n

To see if gut fungi may affect how well radiation therapy works in people, the team measured levels of a protein called Dectin-1 in samples taken from human tumors. Dectin-1, a protein that is found on the surface of some immune cells, is one of the main tools the human body uses to sense the presence of fungi.<\/p>\n

People with higher levels of Dectin-1 in their breast or melanoma tumors tended to have worse survival than those with lower levels, they found. Going back to mice, the researchers found a corresponding result: Tumor cells in mice engineered to lack Dectin-1 were more vulnerable to radiation therapy. <\/p>\n

While the mechanisms behind these observations are still unclear, Dectin-1 may mediate the response to radiation therapy, depending on the levels of fungi that it senses, Dr. Underhill explained.<\/p>\n

Targeting the Microbiome<\/h2>\n

So how could something as seemingly unrelated as the body sensing a change in gut fungi impact the immune response after radiation therapy? <\/p>\n

\u201cThat\u2019s the $20,000 question,\u201d said Dr. Underhill. \u201cBut what I think this study does is put up a kind of red flag saying: \u2018Let\u2019s make sure we understand the fungi in the microbiome, because it could be having important effects on the immune response.\u2019\u201d<\/p>\n

Researchers have already begun to test whether tweaking the composition of the gut microbiome can boost the effectiveness of some cancer treatments. In a recent study, making wholesale changes in the makeup of the gut microbiome<\/a> improved how well an immunotherapy drug worked in some people with melanoma.<\/p>\n

But scientists would like to try adjusting the microbiome in a more specific manner. For this, \u201cwe need to understand which microbial species are most relevant\u201d to cancer treatment responses<\/a>, said Dr. Ahmed.<\/p>\n

\u201cIt would be really handy to be able to characterize a patient\u2019s microbiome\u2014both bacterial and fungal\u2014 and determine their expected prognosis<\/a>, or how they\u2019ll respond to radiation therapy, chemotherapy, or immunotherapy,\u201d added Dr. Underhill. \u201cThen we\u2019d like to see whether it\u2019s feasible to change that microbiome to make those therapies work better.\u201d<\/p>\n

Proteins such as Dectin-1 could potentially serve as biomarkers<\/a> to identify people with a potentially unfavorable microbiome for future clinical trials<\/a>, Dr. Ahmed said.<\/p>\n

\u201cI don\u2019t think we\u2019re too far away from that; I think human studies [targeting specific microbes before cancer treatment] are in the not-so-distant future,\u201d added Dr. Underhill. <\/p>\n

For now, Dr. Ahmed cautioned, people undergoing cancer treatment should avoid any temptation to tweak their gut microbes on their own with over-the-counter<\/a> probiotic<\/a> supplements or prescription drugs. <\/p>\n

\u201cWe don\u2019t want people going out and taking antifungal drugs, because we don\u2019t have evidence yet that that would be helpful, and there could be reasons that it could be dangerous,\u201d agreed Dr. Underhill.<\/p>\n

On the flip side, if people undergoing cancer treatment are prescribed antibiotics, \u201cthat\u2019s for a reason, and they\u2019re going to be important,\u201d he added, and they shouldn\u2019t be skipped.<\/p>\n

Source<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"

September 2, 2021, by NCI Staff Fungi in the gut (purple) may affect how tumors respond after radiation therapy by disrupting the immune system’s response to the cancer. Credit: Centers for Disease Control and Prevention\/Stephanie Rossow Many studies have shown that bacterial communities in the gut may influence cancer in humans, from how fast tumors […]<\/p>\n","protected":false},"author":2,"featured_media":27408,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_monsterinsights_skip_tracking":false,"footnotes":""},"categories":[5137],"tags":[],"class_list":["post-27407","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-world-news"],"_links":{"self":[{"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/posts\/27407","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/comments?post=27407"}],"version-history":[{"count":1,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/posts\/27407\/revisions"}],"predecessor-version":[{"id":43640,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/posts\/27407\/revisions\/43640"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/media\/27408"}],"wp:attachment":[{"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/media?parent=27407"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/categories?post=27407"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/tags?post=27407"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}