You may not realize it, but your body is home to a lot of microbes — way more than you might think. In healthy humans, “microbial cells outnumber human cells by about ten to one,” according to the Human Microbiome Project of the National Institutes of Health.
Most of them, called gut flora, live in your digestive system, especially in the colon. Others live in distinct communities in and on your body, in different types of environments — hot or cold, moist or dry.
If that makes you feel creepy, relax. While some microbes can make you sick — specific bacteria and viruses, for example — most are harmless, and many actually help keep you healthy. Together they make up your microbiome.
Listen in as Emese Zsiros, MD, discusses the exciting whole new area of research on gut flora, how what’s going on in our gut has a huge influence on overall health and happiness, and that our main goal is to look for new approaches that may improve survival for our patients and minimize side effects of treatment.
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Recent Research on Gut Flora
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Learn more about Emese Zsiros, MD, PhD
Emese Zsiros, MD, PhD
Emese Zsiros, MD, PhD, is an assistant Professor of Oncology, Department of Gynecologic Oncology at Roswell Park Comprehensive Cancer Center.Learn more about Emese Zsiros, MD, PhD
Transcription:
Recent Research on Gut Flora
Bill Klaproth (Host): Can the microbes inside you affect the success of your cancer treatment? Here to share with us her recent research on Gut Flora is, Dr. Emese Zsiros, assistant professor of Oncology, Department of Gynecologic Oncology at Roswell Park Comprehensive Cancer Center. Dr. Zsiros, thanks for your time. First off, what are microbiomes and how can may affect your health?
Dr. Emese Zsiros (Guest): Thank you so much for your views. So, Microbiomes are collection of bacteria, viruses and fungi that live in our human body. They mostly live in our gut, and also, can be found in our skin, and essentially in their mouth. And also, in your urogenital system. So, these bacteria’s and small organisms, typically have a lot of beneficial effect in our health, based only curly with how are immune responses work in our body. How do you recognize cancer cells, and how have you responded to certain treatment? So, this is mainly a collection of millions of bacteria that live in our body, and has a strong effect on how we behave and how we develop certain diseases and how we respond to cancer treatment.
Bill: So, these are the good bacteria that we all have in our bodies?
Dr. Zsiros: So, typically most of them are considered to be a good bacteria. However, if there is an imbalance in between the different bacterial types, they can be harmful, and they can actually lead to imbalances, and lead to several different types of diseases, such as obesity, metabolic disorder. Also, some psychiatric diseases have been linked to keeping the balance, and also, cancer or infectious disease.
Bill: So, how does the microbiome, then affect the cancer treatment for certain individuals?
Dr. Zsiros: We don't fully understand the mechanism exactly, but The National Institute of Health really became interested in researching the microbiome around 2007, and launched a Human Microbiome Project, which is aiming to characterize all these bacteria, which are thousands of them that live in our system, and try to understand that, why certain people with a certain composition do develop certain type of diseases, and why a certain composition is associated with better survival in cancer patients. We are learning about her patients by collecting samples from their stall skin, and different sites in their body to try to understand what type of bacteria is necessary for us to have a good immune response, and recognize cancer cells efficiently in our body.
Bill: And, Dr. Zsiros, you've been conducting a clinical trial for patients with ovarian cancer whose disease has returned after treatment. Can you give us an update on that?
Dr. Zsiros: Ovarian cancer is a very rare, but also very deadly disease, and every single year over 14000 patient dies in the United States from ovarian cancer. Typically, we use chemotherapy and the combination with surgery to achieve remission, however most of the patients who get diagnosed with advanced stage disease will recur, and eventually succumb to their disease. So, we're very eager to find new treatment options, and, as you know, immunology and even immuno-oncology is advancing. We're trying to advance the treatment for our patients as well.
So, currently we have a new clinical trial that is trying to activate the patient's immune system by using a combination of three medications, one is Pembrolizumab (Keytruda) which is an immune checkpoint inhibitor which aims to activate the patient's immune system, to be able to recognize the cancer cells more efficiently, and then, this drug is combined with two additional medication. One is called Bevacizumab (Avastin) which is a monoaural anti-body that is trying to improve the blood vessels around the tumor cells, so the immune cells can actually migrate through these vessels, and get into the tumor microenvironment, which is often a problem in tumor immunology. That we don't have the immune cells within the cancer cells, and then the third medication is called oral Cytoxan, which is aiming to tip the balance between their regulatory immune cells that typically would promote tolerance, so the patient would not recognize the cancer cells, and try to aim the good immune cells, the effector or T-cells, to recognize the cancer cells more efficiently, and to be at higher number in the circulation. So, this is a combination of these three medications together, that we believe are needed in combination, to achieve the best possible immune response in ovarian cancer patients.
Bill: So, this study and research then is quite groundbreaking.
Dr. Zsiros: So, no one has done this combination together in this patient population, and we know that using the checkpoint inhibitor to Bevacizumab alone as a single agent, only about 12 percent of the patients showed any kind of response, so this is very dismal. So, they’re hoping that that the triple combination would help us to further activate the immune cells, but also get them into the cancer cells, that a cancer site more efficiently.
Bill: So, can you tell us more about the Center for Immunotherapy, and the important research that's taking place there.
Dr. Zsiros: So, the Center for immunotherapy is located within Roswell Park Cancer Institute, and the main goal of this center is to develop novel therapeutics for patients with solid tumors. We don't just focus on ovarian cancer patients, however that is one of our major focus currently, but also trying to develop new vaccines, drug combinations that have not been tried in cancer patients, and try to optimize the drug delivery and minimize side effect. And we're also trying to select ward optimal patients, who should be receiving therapy.
Bill: So, we started out talking about the microbiome. So, the microbiome and immunotherapy are linked together?
Dr. Zsiros: So, our understanding so far about the human microbiome that from birth, they play a very important role, how our immune system develops and evolves over the years. And typically, the human-microbiome, and the bacteria that they harbor in our guts gets matured around age two to three. We know that diet, lifestyle, sleep, exercise, different genetic background can a modify it slightly, but it really determines how our immune system responds to infections, as well as new cells, such as cancer cells.
The immune system is a very key component of cancer treatment, and to keep the cancer cells from coming back, and from recurring, particularly in ovarian cancer patient, which is a huge problem. We're trying to understand what kind of microbiome our patients have. So, we’re the first sight that actually conducts a detailed microbiome research about ovarian cancer patients, by getting routine samples, which are skin samples, vaginal samples and stool samples, when they're going through immunotherapy treatment. And as they continue with their treatment with us, we resample them every three months, to make sure we understand how the microbiomes are changing in their body, if they are changing, and if there are certain patients, respond really well to immunotherapy, we try to characterize, which are the good bacteria’s that live in their bodies, that might be contributing to the excellent response to immune therapeutic agents. As of right now, we have been collecting specimens on our patients, and we're yet to analyze these results in the next couple of months.
Bill: And when it comes to the microbiome and immunotherapy, do you see this becoming more commonplace, this type of treatment?
Dr. Zsiros: Yes. So, we have a very strong animal data supporting that, mice with a certain bacteria composition respond really well to immune checkpoint inhibitors and new immunotherapy drugs. And there are mice who lack certain types of bacteria, and do not respond at all. And we also know that certain bacterial composition will lead to much quicker tumor growth, in one type of mice and other type of mice purchased from a different location or from a different vendor would grow the tumor tissue in a very different rate. So, these are new findings that were published in 2015 and 2016 in animal models.
So, now this is a very active area of research to find out what happens to human who go…who have cancer and undergo cancer treatment, particularly with immune therapeutic agents. We don't have any solid data currently published, even in another cancer type. So, this is an inventive area, this is a very active area of investigation in patients with melanoma, lung cancer, colorectal cancer, as well as breast and ovarian cancer. So, as of right now, we’re still in early phase and early stage, we have standardized way of how to collect a specimen, and store them properly, so we can identify the different type of bacteria’s. Now we have the ability from our information technology to sequence these bacteria’s, and give us a clear picture of every single one of our patients.
Bill: So a lot of potential uses and very promising that's for sure. Well, Dr. Zsiros, thank you so much for talking to us today about the microbiome and immunotherapy. For more information visit, RoswellPark.org, that's RoswellPark.org. You're listening to Cancer Talk with Roswell Park Comprehensive Cancer Center. I'm Bill Klaproth, thanks for listening.
Recent Research on Gut Flora
Bill Klaproth (Host): Can the microbes inside you affect the success of your cancer treatment? Here to share with us her recent research on Gut Flora is, Dr. Emese Zsiros, assistant professor of Oncology, Department of Gynecologic Oncology at Roswell Park Comprehensive Cancer Center. Dr. Zsiros, thanks for your time. First off, what are microbiomes and how can may affect your health?
Dr. Emese Zsiros (Guest): Thank you so much for your views. So, Microbiomes are collection of bacteria, viruses and fungi that live in our human body. They mostly live in our gut, and also, can be found in our skin, and essentially in their mouth. And also, in your urogenital system. So, these bacteria’s and small organisms, typically have a lot of beneficial effect in our health, based only curly with how are immune responses work in our body. How do you recognize cancer cells, and how have you responded to certain treatment? So, this is mainly a collection of millions of bacteria that live in our body, and has a strong effect on how we behave and how we develop certain diseases and how we respond to cancer treatment.
Bill: So, these are the good bacteria that we all have in our bodies?
Dr. Zsiros: So, typically most of them are considered to be a good bacteria. However, if there is an imbalance in between the different bacterial types, they can be harmful, and they can actually lead to imbalances, and lead to several different types of diseases, such as obesity, metabolic disorder. Also, some psychiatric diseases have been linked to keeping the balance, and also, cancer or infectious disease.
Bill: So, how does the microbiome, then affect the cancer treatment for certain individuals?
Dr. Zsiros: We don't fully understand the mechanism exactly, but The National Institute of Health really became interested in researching the microbiome around 2007, and launched a Human Microbiome Project, which is aiming to characterize all these bacteria, which are thousands of them that live in our system, and try to understand that, why certain people with a certain composition do develop certain type of diseases, and why a certain composition is associated with better survival in cancer patients. We are learning about her patients by collecting samples from their stall skin, and different sites in their body to try to understand what type of bacteria is necessary for us to have a good immune response, and recognize cancer cells efficiently in our body.
Bill: And, Dr. Zsiros, you've been conducting a clinical trial for patients with ovarian cancer whose disease has returned after treatment. Can you give us an update on that?
Dr. Zsiros: Ovarian cancer is a very rare, but also very deadly disease, and every single year over 14000 patient dies in the United States from ovarian cancer. Typically, we use chemotherapy and the combination with surgery to achieve remission, however most of the patients who get diagnosed with advanced stage disease will recur, and eventually succumb to their disease. So, we're very eager to find new treatment options, and, as you know, immunology and even immuno-oncology is advancing. We're trying to advance the treatment for our patients as well.
So, currently we have a new clinical trial that is trying to activate the patient's immune system by using a combination of three medications, one is Pembrolizumab (Keytruda) which is an immune checkpoint inhibitor which aims to activate the patient's immune system, to be able to recognize the cancer cells more efficiently, and then, this drug is combined with two additional medication. One is called Bevacizumab (Avastin) which is a monoaural anti-body that is trying to improve the blood vessels around the tumor cells, so the immune cells can actually migrate through these vessels, and get into the tumor microenvironment, which is often a problem in tumor immunology. That we don't have the immune cells within the cancer cells, and then the third medication is called oral Cytoxan, which is aiming to tip the balance between their regulatory immune cells that typically would promote tolerance, so the patient would not recognize the cancer cells, and try to aim the good immune cells, the effector or T-cells, to recognize the cancer cells more efficiently, and to be at higher number in the circulation. So, this is a combination of these three medications together, that we believe are needed in combination, to achieve the best possible immune response in ovarian cancer patients.
Bill: So, this study and research then is quite groundbreaking.
Dr. Zsiros: So, no one has done this combination together in this patient population, and we know that using the checkpoint inhibitor to Bevacizumab alone as a single agent, only about 12 percent of the patients showed any kind of response, so this is very dismal. So, they’re hoping that that the triple combination would help us to further activate the immune cells, but also get them into the cancer cells, that a cancer site more efficiently.
Bill: So, can you tell us more about the Center for Immunotherapy, and the important research that's taking place there.
Dr. Zsiros: So, the Center for immunotherapy is located within Roswell Park Cancer Institute, and the main goal of this center is to develop novel therapeutics for patients with solid tumors. We don't just focus on ovarian cancer patients, however that is one of our major focus currently, but also trying to develop new vaccines, drug combinations that have not been tried in cancer patients, and try to optimize the drug delivery and minimize side effect. And we're also trying to select ward optimal patients, who should be receiving therapy.
Bill: So, we started out talking about the microbiome. So, the microbiome and immunotherapy are linked together?
Dr. Zsiros: So, our understanding so far about the human microbiome that from birth, they play a very important role, how our immune system develops and evolves over the years. And typically, the human-microbiome, and the bacteria that they harbor in our guts gets matured around age two to three. We know that diet, lifestyle, sleep, exercise, different genetic background can a modify it slightly, but it really determines how our immune system responds to infections, as well as new cells, such as cancer cells.
The immune system is a very key component of cancer treatment, and to keep the cancer cells from coming back, and from recurring, particularly in ovarian cancer patient, which is a huge problem. We're trying to understand what kind of microbiome our patients have. So, we’re the first sight that actually conducts a detailed microbiome research about ovarian cancer patients, by getting routine samples, which are skin samples, vaginal samples and stool samples, when they're going through immunotherapy treatment. And as they continue with their treatment with us, we resample them every three months, to make sure we understand how the microbiomes are changing in their body, if they are changing, and if there are certain patients, respond really well to immunotherapy, we try to characterize, which are the good bacteria’s that live in their bodies, that might be contributing to the excellent response to immune therapeutic agents. As of right now, we have been collecting specimens on our patients, and we're yet to analyze these results in the next couple of months.
Bill: And when it comes to the microbiome and immunotherapy, do you see this becoming more commonplace, this type of treatment?
Dr. Zsiros: Yes. So, we have a very strong animal data supporting that, mice with a certain bacteria composition respond really well to immune checkpoint inhibitors and new immunotherapy drugs. And there are mice who lack certain types of bacteria, and do not respond at all. And we also know that certain bacterial composition will lead to much quicker tumor growth, in one type of mice and other type of mice purchased from a different location or from a different vendor would grow the tumor tissue in a very different rate. So, these are new findings that were published in 2015 and 2016 in animal models.
So, now this is a very active area of research to find out what happens to human who go…who have cancer and undergo cancer treatment, particularly with immune therapeutic agents. We don't have any solid data currently published, even in another cancer type. So, this is an inventive area, this is a very active area of investigation in patients with melanoma, lung cancer, colorectal cancer, as well as breast and ovarian cancer. So, as of right now, we’re still in early phase and early stage, we have standardized way of how to collect a specimen, and store them properly, so we can identify the different type of bacteria’s. Now we have the ability from our information technology to sequence these bacteria’s, and give us a clear picture of every single one of our patients.
Bill: So a lot of potential uses and very promising that's for sure. Well, Dr. Zsiros, thank you so much for talking to us today about the microbiome and immunotherapy. For more information visit, RoswellPark.org, that's RoswellPark.org. You're listening to Cancer Talk with Roswell Park Comprehensive Cancer Center. I'm Bill Klaproth, thanks for listening.