{"id":11932,"date":"2019-09-09T12:00:00","date_gmt":"2019-09-09T12:00:00","guid":{"rendered":"https:\/\/www.cancer.gov\/news-events\/cancer-currents-blog\/2019\/pancreatic-cancer-tumor-microbiome-survival"},"modified":"2024-11-03T15:17:09","modified_gmt":"2024-11-03T15:17:09","slug":"to-treat-pancreatic-cancer-mouse-study-suggests-altering-tumor-microbiome","status":"publish","type":"post","link":"https:\/\/ogkologos.com\/en\/to-treat-pancreatic-cancer-mouse-study-suggests-altering-tumor-microbiome\/","title":{"rendered":"To Treat Pancreatic Cancer, Mouse Study Suggests Altering Tumor Microbiome"},"content":{"rendered":"

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Altering the composition of the tumor microbiome may be a way to improve the treatment of pancreatic cancer, a new study in mice suggests.<\/p>\n

Credit: University of Texas MD Anderson Cancer Center<\/p>\n<\/div>\n<\/figcaption><\/figure>\n<\/div>\n

Many cancer studies focus on the genetic changes in a tumor that may influence its development or identify potential targets for new treatments. But a growing number of researchers have been looking into a different factor that might affect how tumors behave: bacteria<\/a>.<\/p>\n

Several studies have suggested that the mix of bacteria in the gut of people with cancer\u2014their gut microbiome<\/a>\u2014can affect their immune system\u2019s<\/a> ability to recognize and attack tumors or the effectiveness of some cancer treatments. Now, results from a new study suggest that, in the case of people with pancreatic cancer<\/a>, the makeup of bacteria that populate their tumors could predict how long they live<\/a>.<\/p>\n

Experiments in mice conducted as part of the study also pointed to the possibility that fecal transplants\u2014which are primarily used to treat people with a serious infection with a particular type of bacteria\u2014might have potential as a way to treat pancreatic cancer.\u00a0<\/p>\n

Findings from the NCI-supported study, led by researchers at the University of Texas MD Anderson Cancer Center and Johns Hopkins Kimmel Cancer Center, were published August 7 in Cell<\/em>.<\/p>\n

Based on the results, an early-stage clinical trial is being planned to test fecal transplants in people with pancreatic cancer.\u00a0<\/p>\n

While the study\u2019s findings are encouraging, said the study\u2019s lead investigator, Florencia McAllister, M.D., of MD Anderson\u2019s Department of Clinical Cancer Prevention, she cautioned that it\u2019s still too early to say what will come of them.<\/p>\n

At the same time, Dr. McAllister added, the findings point to wide-ranging possibilities for altering the tumor microbiome in people with this highly fatal form of cancer. \u201cI think it\u2019s something that could have an impact on any strategy that\u2019s being thought about for pancreatic cancer treatment,\u201d she said.<\/p>\n

Building on Earlier Research<\/h2>\n

Mounting evidence shows that there is a complex relationship between the microbes in a person\u2019s body\u2014primarily those in the gastrointestinal tract<\/a>, or gut, where the majority of the bacteria in the body reside\u2014and the formation and development of cancer.\u00a0<\/p>\n

One recent study, for example, found that the composition of the gut microbiome appears to affect the efficacy of immunotherapy drugs in people with melanoma<\/a>. Another study, from NCI researchers, showed that the makeup of the gut microbiome can influence the immune response to tumors in the liver<\/a>.<\/p>\n

Dr. McAllister and her colleagues, which also included researchers from Texas Southern University and the Weizmann Institute of Science in Israel, wanted to look more closely at the microbiome in people with pancreatic cancer\u2014in particular, the bacteria in their tumors\u2014and whether it might be a factor in the poor prognosis<\/a> of people diagnosed with the disease. To do so, they turned to the rare group of people diagnosed with pancreatic cancer who live for a long period.\u00a0<\/p>\n

The study, the research team wrote, builds on data from other recent studies of long-term survivors of pancreatic cancer.<\/p>\n

One study, for instance,\u00a0failed to find differences in mutations found in common cancer-associated genes<\/a> that might potentially account for why some people live longer. And another identified the same proteins on tumor cells that can induce an immune response<\/a> as those that are produced in response to bacterial infections<\/a>.<\/p>\n

According to Laura Wood, M.D., Ph.D., a member of the research team from Johns Hopkins, these latter findings suggest a scenario where, absent any noteworthy genetic differences between the tumors in long- and short-term survivors, perhaps there is a bacterial component at play.<\/p>\n

In long-term survivors, Dr. Wood\u00a0said, maybe \u201ctheir immune systems are already primed by [their microbiome] to respond to tumors.\u201d<\/p>\n

A Bacterial Survival \u201cSignature\u201d<\/h2>\n

The team began with a group of people treated at MD Anderson who had undergone surgery for their disease. The group included 21 long-term survivors (median survival<\/a> of 10.1 years) and 22 short-term survivors (median survival of 1.6 years) who were matched to the long-term survivors based on age, sex, treatments received, and other factors.\u00a0<\/p>\n

The researchers found a far greater diversity in the type of bacterial species in the tumors of the long-term survivors than in those of the short-term survivors. To validate those findings, they looked at a similar cohort of long- and short-term survivors who had been treated at Johns Hopkins. They saw the same pattern: long-term survivors had a greater diversity of bacterial species in their tumors.<\/p>\n

In the MD Anderson group, they were also able to identify a \u201cbacterial signature\u201d\u2014a group of bacteria that, when collectively present at high levels, could predict which patients had been long-term survivors. As with the bacterial diversity finding, the same signature was seen in long-term survivors from the Hopkins group.<\/p>\n

And, consistent with the idea that the microbiome was exerting its effect by influencing the immune response, tumors of long-term survivors also tended to have much higher numbers of cell-killing T cells<\/a> than tumors in short-term survivors.<\/p>\n

Analysis of stool and tissue samples collected from three long-term survivors in the MD Anderson cohort revealed something else: There were no similarities between the bacterial communities seen in healthy tissue near pancreatic tumors and those present in the gut. But approximately one-fifth of the bacterial species in tumors were also present in the gut.
The finding, the research team wrote, suggests a bacterial migration from the gut to the tumor.\u00a0<\/p>\n

Turning to Fecal Transplants<\/h2>\n

If bacteria can migrate from the gut to the pancreas, Dr. McAllister said, that raises the question of whether it\u2019s possible to alter the microbiome of pancreatic tumors so that they resemble those of long-term survivors.<\/p>\n

To begin to answer that question, the research team tested fecal transplants in mice. In humans, fecal transplants have cured gastrointestinal tract infections with the bacteria C. difficile that won\u2019t respond to existing antibiotics. The transplants, which come from healthy donors, introduce a new community of bacteria into the patient\u2019s gut that, through mechanisms that aren\u2019t well understood, resolve the C. difficile infection.<\/p>\n

The team began by eliminating as much of the existing microbiomes as possible in tumor-free mice by treating them with antibiotics. The mice then underwent fecal transplants using fecal material not from other mice, but from one of three groups of people: those currently being treated for advanced pancreatic cancer, long-term survivors who had no evidence of cancer, and healthy volunteers. Finally, the mice were implanted with tumor cells taken from mice engineered to develop pancreatic cancer.\u00a0<\/p>\n

When the researchers assessed the mice 5 weeks later, they found that the tumors were largest in mice that received a fecal transplant from patients with active cancer and smallest in mice that received fecal transplants from long-term survivors. Transplants from healthy volunteers also slowed tumor growth, but not to the same extent as those from long-term survivors.\u00a0<\/p>\n

The researchers also found that tumors in mice given fecal transplants from the long-term survivors had more cell-killing T cells in and around their tumors, whereas tumors in mice that received transplants from people with advanced pancreatic cancer had higher levels of a type of immune cell that holds back an immune response.\u00a0<\/p>\n

Finally, treating\u00a0mice that received fecal transplants from long-term survivors with antibodies<\/a> that blocked T cells negated the impact on\u00a0tumor growth.<\/p>\n

Building the Evidence<\/h2>\n

William Hawkins, M.D., who directs the NCI-funded Specialized Program of Research Excellence for pancreatic cancer at Siteman Cancer Center in St. Louis, called the study\u2019s findings promising. But he cautioned that there is still much more to learn.<\/p>\n

Given all that\u2019s been unearthed about the affect of a person\u2019s microbiome on their health, Dr. Hawkins said he wasn\u2019t surprised to see an association between certain bacteria in the tumor and survival.<\/p>\n

\u201cBut you have to ask the question: Is it causative, is it an effect, or is it somewhere in between?\u201d<\/p>\n

Regardless of what role the bacterial communities in a tumor play, Dr. Wood pointed to the potential of using the bacterial signature found in the study as a biomarker<\/a> of expected\u00a0survival. Although it needs to be validated in other studies, she stressed, \u201cI think that has potentially clinical utility in and of itself.\u201d<\/p>\n

As for fecal transplants, this new study is not the first to investigate their potential role in cancer treatment.\u00a0<\/p>\n

In a study published last year, French researchers showed that fecal transplants could improve the efficacy of immune checkpoint inhibitors in mouse models of sarcoma and kidney cancer<\/a>. And another research group at MD Anderson saw similar results with fecal transplants<\/a> in combination with immune checkpoint inhibitors in mouse models of melanoma.<\/p>\n

The early-phase clinical trial at MD Anderson will use fecal material from healthy donors, Dr. McAllister explained. Because it\u2019s an early-phase trial, she stressed, it’s primarily focused on the safety of the treatment and better understanding whether some of the tumor microbiome and immune changes seen in preclinical studies<\/a> also occur in humans.<\/p>\n

That a fecal transplant could influence the immune system in humans in some way would not be a surprise, Dr. Hawkins noted. \u201cBut is it going to \u2026 turn some patient\u2019s tumor from an immunologically \u2018cold\u2019 tumor to a \u2018hot\u2019 tumor and help cure them? We\u2019re still some way away from knowing that,\u201d he said.<\/p>\n

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

September 9, 2019, by NCI Staff Altering the composition of the tumor microbiome may be a way to improve the treatment of pancreatic cancer, a new study in mice suggests. Credit: University of Texas MD Anderson Cancer Center Many cancer studies focus on the genetic changes in a tumor that may influence its development or […]<\/p>\n","protected":false},"author":2,"featured_media":11933,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_monsterinsights_skip_tracking":false,"footnotes":""},"categories":[5137],"tags":[],"class_list":["post-11932","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\/11932","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=11932"}],"version-history":[{"count":1,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/posts\/11932\/revisions"}],"predecessor-version":[{"id":44437,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/posts\/11932\/revisions\/44437"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/media\/11933"}],"wp:attachment":[{"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/media?parent=11932"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/categories?post=11932"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/tags?post=11932"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}