Welcome to OncoBites!

Here at OncoBites, a team of graduate scientists and Ph.D.s with a passion for cancer research has gathered to share cutting-edge research with a wider audience. We understand that jargon and isolated professional communities have made science feel inaccessible to most people, even people considering the field. In addition, paywalls on articles can make trying to investigate topics alone a challenge. On the other hand, many social media-targeted articles can over-simplify science and leave readers with more questions than answers, or misunderstandings about how much progress remains before advances reach the clinic.

OncoBites seeks to fill these gaps; we will not oversimplify the science, but we will share research in clear language that takes down the barriers that turn people away from our field. We will not hide when results are preliminary; we want readers to know what is new in the lab and what is new in the clinic, and not to confuse the two. Our articles will be bite-size, approximately five minute reads that share what is exciting in the field of cancer research. We will include links to deeper background information and the full articles we discuss for those who would like to learn more. Initially, we will post weekly, but we hope to increase our frequency as we gain more contributors.

Come join us!


In cancer, your own lymph nodes turn against you

Emily B. Harrison, PhD

Perhaps the only time most people consider their lymph nodes is at a doctor’s office. Often, when examining you, a physician will touch the sides of your neck, feeling for enlarged lymph nodes. In this case, swollen nodes indicate that your body is mounting an immune response. This immune response is the body’s way of mobilizing an attack against an infection, whether bacterial or viral, and swelling indicates the gathering of immune cells for this purpose. However, in the context of cancer, lymph nodes play a more sinister role.

Clinicians and scientists debate the importance of lymph nodes in cancer metastasis, but two new reports shed light on this route of cancer spread

If you or a loved one has ever had cancer, you have already had to consider lymph nodes and their importance in the spread of cancer. The lymphatic system is a drainage system and conduit for the immune system that extends throughout the body.  A primary concern with most cancers is metastasis. Metastasis refers to cancer cells breaking off from the original site or tumor and moving to other places in the body, including the liver, lungs, and brain. Tumors that grow in these secondary sites are called metastases. The presence of metastases means a more serious diagnosis. In fact, the vast majority of cancer-related deaths are attributed to metastases and not the growth of the original tumor.

Upon detection of cancer, the next step is determining how far the cancer has spread. This is in most cases done by removing or biopsying the nearest lymph node, also called the sentinel lymph node, and observing whether there are cancer cells present.  The presence of cancer cells in lymph nodes is a determining factor in the stage, or severity, of cancer. However, there is no consensus in the medical community as to what extent further lymph nodes should be removed. Evidence from clinical trials is mixed. In breast cancer, for example, some studies report that removing more than the sentinel lymph node had no effect on breast cancer patient survival, suggesting that only the sentinel node is clinically important. But others have found that treating regional lymph nodes with radiation early on has a positive impact, implying that nodes beyond the sentinel node do play a role in the spread of disease.

On a more basic level, scientists and clinicians debate whether cancer cells that make it to the lymph node can leave and form metastases in different organs. To better understand how cancer cells can (or cannot) spread from lymph nodes to distant sites, two groups of researchers used mouse cancer models. Their results were published in the March 23rd issue of Science magazine.

In the first study, a group of researchers based out of Austria began by precisely injecting breast cancer cells into a lymph node and observing what happened. They found that the tumor cells quickly grew and crawled toward the small blood vessels within the node itself. After just three days, the researchers could detect cancer cells in the blood and after eleven days they found that cancer cells had spread to the lungs. These results demonstrated that yes, cancer could metastasize from the lymph node to other places in the body.

The researchers then tested to see whether the cancer cells got to the lungs directly from the first lymph node, or if they took a more indirect route through other downstream nodes. To do this, they tied off the vessel carrying lymph fluid from the first node to the second, effectively limiting the path the cancer could take so that it could only travel out of the node via the bloodstream. Still, the cancer cells spread to the lungs. They also observed that in human breast cancer patients, cancerous cells were present in the blood vessels surrounding sentinel nodes. Based upon their evidence, it would seem that at least in mice, cancer cells can and do spread from lymph nodes by entering blood vessels within the node and traveling via the bloodstream to more distant sites in the body, such as the lungs.

In the second study, a group of researchers based out of Harvard used a different approach to answer the same question. Their method used a fluorescent protein found in coral called Dendra2  to visualize cancer cells as they moved to different places in the mice. This protein has an interesting and useful property in that it normally glows green, but turns red if hit with a blue laser. Knowing this, the researchers genetically engineered cancer cells to express this protein, and then injected the cells into the breast of the mouse. Once the tumor cells grew and metastasized, the team shined a blue laser on the nearest lymph node, turning cancer cells in that specific location red. From there, they looked for the red-colored cells (from the node) in various other places in the mice. They found these specific cells in the blood and in the lungs, indicating that the cells had left their original location and formed tumors elsewhere. Like the previous research group, they found that cancer cells crawl towards and into lymph node blood vessels. The conclusions from both groups are strikingly similar, both point to the lymph nodes as a conduit for cancer metastasis.

While these studies provide important insights, there are still questions left to address. For one, does cancer behave the same way in people? Also, what does this mean for treatment of cancer patients? On a personal level, I’ve had to ask many of these same questions. My own mother was diagnosed with breast cancer and recurrent melanoma; she is now a 7-year survivor. At the time of diagnosis the decision was made to remove all the lymph nodes in her right arm. This has left her with long-term consequences. She now suffers from lymphedema, swelling caused by fluid build-up due to the lack of nodes. And while she tells me it is not painful, she does have to wear a special sleeve and use a pump to help alleviate the swelling. As a side effect of the lymph node removal, she also needs to be especially wary of infection, as that arm does not have a fully operational immune system. Even with all these complications, she is simply glad to have survived. For all we know, removing the nodes may have been what saved her. Like millions of cancer patients and their families around the world, we may never truly know which care decisions ultimately made a difference in her outcome.

Advancements in cancer research, like the aforementioned studies, are key to understanding what cancer is doing in the body. The results from these experiments will undoubtedly lead to even more research in the area. My own research group at the University of North Carolina is studying this very subject: attempting to understand the importance of lymph nodes in cancer metastasis. In the end, I believe we all have the same goal—for more people to survive cancer. To do that, we need to understand how and where cancer moves so that we can stop it in its tracks.

Works Discussed

  1. Brown, M., Assen, F. P., Leithner, A., Abe, J., Schachner, H., Asfour, G., … & Kerjaschki, D. (2018). Lymph node blood vessels provide exit routes for metastatic tumor cell dissemination in miceScience359(6382), 1408-1411.
  2. Pereira, E. R., Kedrin, D., Seano, G., Gautier, O., Meijer, E. F., Jones, D., … & Beech, E. (2018). Lymph node metastases can invade local blood vessels, exit the node, and colonize distant organs in miceScience359(6382), 1403-1407.

Image Credits

Breast and Adjacent Lymph Nodes. Source: National Cancer Institute (NCI), Creator: Don Bliss (Illustrator)


What exactly is cancer?

Sara Musetti

I came to a realization this week. Here at OncoBites, we made a cancer research blog and then… forgot to tell our readers what cancer is. And I know, most of you reading are thinking “I know what cancer is!” because you read about it all the time. And maybe, if you’re a cancer researcher, or a biology student, or you did a lot of reading when cancer first touched your life–because cancer has touched most of our lives, by now–maybe you do have a good idea of what cancer is. But maybe you just have a vague sense of what cancer is, and we jumped in telling you that the bacteria in your gut can affect its treatment, or the proteins in your tumor can change it, and you thought… wait, what proteins are in tumors? How do bacteria play a role? What’s really going on there?

And for that, I apologize. Mea culpa. We owe you an explanation of what cancer really is, and why it’s so hard to treat, before we get any farther into all the amazing ways scientists are trying to cure it. Because it’s complicated, and messy, and it really does require some truly fascinating work.

International symbol for carcinogens, mutagens, or reproductive hazards

So, to begin, let’s talk about how we first get tumors. Morgan, rightly, went back and explained some of the risk factors around us that cause cancer, and how we can avoid them. You should check that out. But we also have to touch on how those risk factors cause cancer. Cancers arise due to mutations in certain genes–I say certain, because not all mutations will cause cancer. Genes replicate all the time, and sometimes mistakes are made. Mistakes can happen naturally, or they can be the cause of a mutagen, an outside force that acts on a cell and produces a mutation. Mutagens can be UV rays from the sun, alcohol, chemicals in charred meat, etc. Most of the time, mutations are repaired, but sometimes they are not, and sometimes the uncorrected mistakes are even passed on to offspring. Sometime early in history, a mutation changed eye color in some from brown to blue, and gave eye doctors the chance to admonish me on wearing sunglasses at all times to protect my pale eyes (thanks, genes!). But some mutations, especially those in the cellular mechanisms that control how we fix errors in our DNA, or how cells decide to grow or stop growing, can lead to cancer. If a cell accumulates errors in these pathways, the begin to grow uncontrollably, and accumulate more mutations because they can’t fix them, and then you have a cancer cell, and that cell seeds a tumor.

Breast Tumor Microenvironment. Tumor cells are indicated in cyan, collagen in green, and macrophages in red 

Now comes the hard part. Tumors are far more than just a cell that messed up and started growing out of control. If that’s all it was, scientists could treat it. But remember, cancer cells have lived inside you as perfectly normal cells for years. They know your body, and more importantly, your body knows it. Your body, particularly your immune system, which deals with internal threats,  thinks it’s you, and that you’re growing like that for a reason. Think of tumor cells almost like Russian sleeper agents–they spent years living alongside other cells, watering their garden  filtering toxins from your blood in the liver or producing milk in the breast. They know all the signs to make your immune system trust it, and to make your immune system stand down. And that means that oftentimes, your immune system won’t try to stop it until it has lots of mutations. And once it has lots of mutations, cancer cells are busy finding new ways to protect themselves. They know all the secret handshakes, remember, so they call up other cells to come and protect them. Cancer cells recruit fibroblasts, cells that produce collagen and a fibrous mesh that surround tumors and shield them from the immune system or drugs. They bring in macrophages that help orchestrate immune responses, which then send out signals not to let the immune system in. All these cells (and more!) are constantly talking to each other by sending out little chemicals and proteins that tell each other to keep growing, to build new blood vessels, to pump chemotherapy drugs out of the cells, and to keep suppressing the

Killer T cells surround a cancer cell. T cells, the immune cells responsible for eradicating disease, are shown surrounding a cancer cell (center)

immune system. Tumors are dynamic, with many groups of cells working together in a soup of proteins and fibers (called the microenvironment) to stay alive at all costs. If the immune system does make it all the way into the tumor, past all the signals telling it to turn back and past the walls of fibers, the cancer cells still have one trick up their sleeve, and it works very well. Your immune system is good at telling the difference between your cells and other cells (this is why the risk of rejection after organ transplant is so high), but if it ever makes a mistake, cells have a protein on their surface, Programmed Death Ligand-1 (PD-L1) that binds with its partner, Programmed Cell Death Protein 1 (PD-1), on immune cells (specifically T cells) and inhibits immune cells so they do not kill the cell. Unfortunately, tumors use this signal to further suppress the body’s ability to fight cancer and continue to grow. (One of the most exciting recent discoveries in cancer therapy has been the advent of checkpoint inhibitors, which block this PD-1/PD-L1 signaling and similar pathways and keep cancer cells from evading the immune system in that way.) Essentially, cancer cells find ways to make your body turn on itself to keep them alive, because that’s what all living things do–they fight to live. And they’re very good at it, because they aren’t spending energy making sure they’re growing right, or repairing their DNA, or ensuring they have enough food. They aren’t even staying in one place–most tumors become the most deadly when they metastasize, or send some cells to go grow in your other organs. And that makes it very hard for scientists to kill a rogue section of your cells without killing you. Cancer isn’t an infection, where bacteria get inside and it’s fairly easy to tell one from the other. Cancer is when your body turns on you, and science does not have a way to safely end that civil war at this time. Worse still, each individual tumor is different, based on the organ it started in, what mutagens caused it, the environment of the body it grew in, the treatments it encounters–no tumors are completely alike. In some, more macrophages are bad for you. In some, they’re good. Some let lots of T cells (the cells that kill tumor cells or infections) in without additional treatment; some have barely any.

None of this is to say that we are without hope. Scientists and clinicians are getting better every day at recognizing the weaknesses in tumors. We’re getting better at testing tumors and choosing treatments that are best suited for certain tumors based on what kinds of cells are in the tumor, or what mutations the tumor cells carry. Treatments are getting smarter as we learn more about how these tumors operate. There probably won’t be one single cure for cancer, because “cancer” is a word we use for hundreds and thousands of unique diseases with a few unifying similarities. But there will be leaps towards cures. And here at OncoBites, we’re going to tell you about them.

Image Credits:

© NIH Image Gallery: Breast Tumor Microenvironment

© NIH Image Gallery: Killer T cells surround a cancer cell

Cancer – how much of it is preventable?

Morgan McSweeney

What percent of cancer cases are due to lifestyle choices or environmental conditions, and are therefore potentially preventable? Take a guess: 10%, 25%, 75%, or 90%? A paper by Anand et. al set out to answer exactly this question nearly ten years ago, pulling data from large-scale epidemiological studies across a large range of cancer types and demographics. That paper has since been cited roughly 1,500 times.

Strikingly, they found that about 90-95% of cancer cases were estimated to be due to environmental conditions and/or life choices, and only 5 to 10% of all cancer cases were estimated to be due to innate genetic traits. What does this mean for us as a society? It suggests that we do not have to wait to receive a cancer diagnosis to begin to take measures to fight against the disease. Perhaps, however, that is a task easier said than done. What specific environmental and lifestyle choices are the strongest contributors to increased cancer risk? Continue reading to find out!


Did you know that about 38% of Americans are obese by clinical standards? We know that being overweight is a risk factor for serious diseases such as heart disease, stroke, and type 2 diabetes, but recently it has become increasingly clear that obesity is also tightly linked to cancer. As it turns out, roughly 14% (in men) and 20% (in women) of all cancer deaths in the United States are due to excess weight/obesity. Certain colon, rectal, breast, ovarian, liver, and cervical cancers have all been linked to being overweight.

How does obesity lead to cancer? Excess fat can alter your body’s production of signaling molecules such as the hormones responsible for blood sugar control, certain inflammatory responses, and sex steroids (hormones). Disturbing these signaling pathways puts your body under a constant state of physiological stress, which contributes to cancer development by sending signals to “promote” the growth of tumor cells which have undergone a mutation and are waiting for the right microenvironment to continue their progression. Consistently, regular physical activity has been extensively and conclusively shown to reduce the risk for a host of cancer types, and even to be beneficial in the recovery of cancer survivors.


The degree to which diet impacts cancer risk varies considerably across cancer types. Overall, diet is estimated to play a causative role in approximately 30-35% of all cancer cases, but do specific food groups have a stronger association with cancer than others? Red meat has been classified by the World Health Organization as a Class 2A carcinogen (i.e., probably cancer-causing), and processed meat has been classified as a Class 1 carcinogen (i.e., definitely cancer-causing). There is evidence to suggest that cooking meat at high temperatures (such as grilling or pan frying) has carcinogenic potential by producing heterocyclic amines that can bind to your DNA and increase risk of tumor development. Bisphenol (BPA) from plastic food containers may leach into food and has been suggested by animal studies to increase the risk of breast and prostate cancers.

Increased consumption of whole grains, vegetables, and legumes has been suggested to decrease cancer incidence. Part of this effect is thought to be due to protective compounds found in these “healthy” foods, and part of the protective effect is thought to come from a corresponding decrease in consumption of “unhealthy” foods. For example, eating more vegetables and legumes might mean that you are replacing the consumption of processed or red meats.


Did you know that there is an association between drinking alcohol and an increased incidence of certain cancers? It is estimated that about 5% of all cancer cases are due to alcohol consumption. Analyses of breast cancer risk and alcohol consumption in a worldwide cohort of women suggested that for every standard drink of alcohol consumed per day, there was roughly a 7% increased relative risk of getting breast cancer (e.g. if your prior estimated actual chance of getting breast cancer was 10%, with one additional drink per day your absolute risk would now be equal to (10)x(1.07)=10.7%). Further, high levels of alcohol intake have been shown to increase your chances of liver and colorectal cancers.

It is thought that in patients who are infected with hepatitis, excessive alcohol consumption can increase the virus’s potential to develop into hepatocellular carcinoma (liver cancer). How does this happen? We know that ethanol and its metabolic byproducts can generate pro-inflammatory molecules and free radicals, which damage surrounding cells, providing a possible opportunity for further infection.


News flash: smoking causes cancer! But how much cancer does it cause? It is estimated that roughly 25-30% of all cancer cases are due to tobacco use. Smoking causes about 20% of the deaths that occur in the U.S. each year and smokers have a life expectancy that is 10 years shorter than non-smokers. Quitting before the age of 40, however, reduces your smoking-related risk of death by about 90%. Since the 1960s, public health efforts have steadily pushed to minimize the use of tobacco products. Even second-hand smoke has been classified by the EPA and the International Agency for Research on Cancer as a Group 1 carcinogen (meaning that there is sufficient evidence of carcinogenicity in humans).

Infectious Disease

Did you know that about 18% of worldwide cancers are associated with infection? In many of those cases, the cancers are a result of infection by a virus (e.g. human papillomavirus – HPV, Epstein Barr virus, HIV, herpes, hepatitis). Some of these viruses are directly mutagenic, meaning that when they turn on their own DNA machinery, it can cause cancer. Other viruses are indirectly mutagenic, meaning that as they go about replicating themselves, they produce molecules that can cause oxidative stress to your DNA, which can contribute to inflammation and eventual mutation. DNA mutations are the underlying cause of cancers.  Vaccinations are available for several viruses that can cause cancer, such as HPV and hepatitis, and represent an efficient, low-risk method for reducing your chance of disease.

Environmental pollution and radiation

As many as 10% of cancer cases are thought to be due to radiation and environmental exposures. The most common source of radiation is UV light from the sun, but medical imaging and other incidental or occupational radiation exposures can additively contribute to considerably increased cancer risk.


Roughly 90-95% of cancers are due to external (and therefore potentially preventable) causes. The scientific consensus on methods for the reduction of cancer incidence is increasingly clear, but that does not necessarily translate to rapid widespread adoption. For decades, it has been public knowledge that smoking and cancer are inextricably linked. However, although smoking is becoming less common, it is still prevalent. In 2016, roughly 15% of adults regularly smoked cigarettes. Similarly, the link between obesity and heart disease, cancer, and diabetes is well-established, yet obesity is at an all-time high. There are also 5-10% of cancers that are a result of genetics.

Completely preventing cancer from occurring appears to be currently beyond our reach. Fortunately, many talented scientific groups and research communities are working on cutting-edge therapeutic strategies to treat this horrible disease once it has begun. Here at Oncobites, we will summarize new strategies, developments, and ideas about how to improve our ability to treat this disease when it does occur.

Work discussed

Anand, P, et al. Cancer is a Preventable Disease that Requires Major Lifestyle Changes. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2515569/. Pharm Res. 2008 Sep; 25(9): 2097–2116. 

Image source: Air Force Materiel Command

Engineering aggressive breast cancer subtype may allow more treatment choices

Manisit Das

Breast cancer may sound like a single disease, but it is not. There are many subtypes of the disease, which guide the course of disease progression and treatment strategy. One of these subtypes, referred to as triple-negative breast cancer (TNBC) is particularly difficult to treat. Recently, researchers at Lund University, Sweden identified a cellular growth factor that may be linked to this aggressive TNBC subtype. Blocking the growth factor in experimental cancer models transformed the tumor into a subtype which is known to have a better clinical outcome. Down the road, this can be a unique therapeutic strategy against TNBC.

A critical step after a diagnosis of breast cancer is to determine the molecular subtype of the tumor. Classification of the tumors is guided by the expression of hormone epidermal growth factor receptor 2 (HER2), estrogen receptors (ER), and progesterone receptors (PR). Testing positive for one of these receptors may make a patient eligible for hormone therapy* or drugs that target a specific receptor, such as HER2. TNBC lacks these receptors, making hormone or receptor-targeted therapies ineffective against this type of cancer. Chemotherapy and radiation are the most common treatments for TNBC patients. In a study recently published in Nature Medicine, senior author Kristian Pietras and his team identified a strategy to change the molecular subtype of TNBC to ER-positive tumors, rendering the cancer sensitive to Tamoxifen, a drug commonly used to treat estrogen receptor-positive breast cancer.

Tumor cells interact strongly with the surrounding environment, referred to as the tumor microenvironment, by transmitting and receiving survival and growth signals. In their work, Dr. Pietras and his team identified a protein of the platelet-derived growth factor family (PDGF-CC), which facilitate communication between cancer and surrounding connective tissue cells like fibroblasts.

Analyzing genetic information from tissue samples of about 900 breast cancer patients, they discovered a strong connection between PDGF-CC expression and poor clinical outcome. To confirm if PDGF-CC expression is important in the progression of breast cancer, the researchers developed a genetically engineered mouse model where they artificially disrupted the expression of PDGF-CC and looked at tumor growth. This way of knocking out a gene is a strategy commonly used by biologists to understand the function of a gene. They observed a poorer tumor growth when mice lacked the PDGF-CC gene. To ensure that this is not due to other developmental defects in the engineered mice, the researchers transplanted fragments of the tumor from the PDGF-CC defective mice to non-engineered mice. About half of the transplants didn’t give rise to tumors. In comparison, transplants from mice which didn’t have the PDGF-CC gene knocked out formed tumors with every attempt.

The researchers next looked into how PDGF-CC expression affects the expression of different genes in the breast tumors. From their experiments, they found that PDGF-CC expression plays a role in influencing the molecular subtype of the breast cancer. They uncovered a positive correlation between PDGF-CC expression and markers of TNBC. This led them to their subsequent experiment, where they tested if blockade of PDGF-CC can switch the subtype of breast cancer.

An antibody was used to block PDGF-CC. Antibodies are large proteins which can be engineered to bind and inhibit other target proteins of interest. Blocking PDGF-CC led to increase in the expression of ER, which indicated a switch in cancer subtype. The inhibition of PDGF-CC by gene knockout or antibody also made the breast tumors sensitive to tamoxifen therapy. The therapeutic benefit was lost when the PDGF-CC gene was artificially introduced into the mice.

It was originally believed that the various subtypes of breast cancer originate from different cells in the mammary gland. However, this study shows that cells in the tumor microenvironment can also directly influence the subtype of cancer, and is tunable by pharmaceutical intervention. This is indeed an exciting development. Nevertheless, there is a considerable journey ahead before this becomes a standard clinical practice. As we are gaining more insights into molecular characteristics of cancer, it is also increasingly evident that there is no such thing as a pure cancer subtype, thanks to intratumor heterogeneity. In other words, there can be considerable variations of cancer cells within a single tumor. Under the circumstances, subtype switching may sensitize one group of cells within the tumor, while not affecting another group of cells. We do not yet know if the cells under PDGF blockade would eventually become resistant by exploiting a compensatory signaling. Thus, there are a lot of questions still to be answered.

TNBC is a particularly aggressive form of cancer more likely to affect young people, African-Americans, Hispanics, and people with inherited mutations that make them susceptible to breast cancer. We sincerely hope that the findings of this study will stimulate a new direction in designing a clinical strategy for patients affected by this aggressive form of breast cancer.

*Author’s note: Hormone therapies for breast cancer slow down the growth of the tumor by cutting off the hormonal supply of the cancer cells. The hormones fuel the growth of hormonal receptor-positive cancers. This strategy is not same, rather opposite of hormone replacement therapy (HRT) used by postmenopausal women to ease symptoms of menopause. In fact, HRT may increase the likelihood of breast cancer.

Work discussed:

Roswall, P., Bocci, M., Bartoschek, M., Li, H., Kristiansen, G., Jansson, S., . . . Pietras, K. (2018). Microenvironmental control of breast cancer subtype elicited through paracrine platelet-derived growth factor-CC signaling. Nature Medicine. doi: 10.1038/nm.4494

From bacteria in your gut to cancer in your skin, everything is connected

Sara Musetti

The word “bacteria” is often accompanied by a nose wrinkled in disgust and thoughts of infection and disease. Even though we have as many microbial cells as human cells within each of us—that’s right, we’re 50% bacteria—most people still find bacteria something to avoid. However, recent research into the gut microbiome, the ecosystem of commensal bacteria and other microbes that colonizes the human gut, suggests that the bacteria inside us may be a key factor in how patients respond to novel cancer treatments. In the January 2018 issue of Science, researchers from the University of Chicago to MD Anderson in Texas to Gustave Roussy Cancer Campus in France published articles detailing how the gut microbiome influences the progression of many cancer types, including colon cancer, lung cancer, and skin cancer. That microbes in the gut could influence cancer in the gut (particularly the colon) was unsurprising and has been studied for some time; however, the fact that microbes thriving in our digestive tract can influence cancer cells in far off locations, such as the skin, was a novel and groundbreaking discovery. Scientists first discovered the fact that bacteria could influence cancer growth by studying the disease progression of patients taking antibiotics compared to patients who were not, and found that patients on antibiotics often suffered from more aggressive disease progression. Wide spectrum antibiotics kill off many species of bacteria, not just the ones making us sick. What scientists found was that by killing off the bacteria that normally live within us and support our health, known as commensal bacteria, cancer cells in colon, lungs, kidney, and skin did not respond to novel immunotherapies such as checkpoint inhibitors, which exploit the immune system to fight cancer. This work implied that some bacteria in the gut can offer some kind of protective effect that helps the body suppress cancer growth or boost immune function, up to a point.

The microbial community in our guts are impacting our health in ways scientists are only just beginning to understand

Checkpoint inhibitors are a new class of drugs that have offered remarkable results to certain patients. For example, President Jimmy Carter was given checkpoint inhibitors to treat his metastatic melanoma when it traveled to his brain in 2015. Within months, he was in remission, a rare and remarkable recovery. Checkpoint inhibitors act by blocking the ability of cancer cells to inactivate killer T cells, the body’s natural response to disease. With checkpoint inhibitors, many patient’s bodies can identify and kill tumor cells through natural immune activity, the way they fight infectious diseases. Immunotherapies are becoming an attractive and promising area of research, and the finding that the gut microbiome can impact their efficacy could be key to expanding their use in the clinic.

While scientists are still unsure of exactly how the gut microbiome is impacting a patient’s response to immunotherapies, the evidence is remarkable. Three scientific teams in three different locations noticed these trends and performed a deep analysis of the microbiome of cancer patients on checkpoint inhibitors. Each noticed that there was greater diversity in the gut microbiomes of patients that respond to checkpoint inhibitors—that is to say, patients with more species of bacteria in their gut were more likely to see positive outcomes from checkpoint inhibitor therapy, including entering remission. Greater microbial diversity has been linked with many health benefits, and now a robust anti-tumor immune response may be one of them. Each team of scientists identified groups of bacteria that were found in patients who responded to therapy versus those who did notAkkermansia, Faecalibacterium, and Bifidobacteriaceae. Working with mouse models of cancer, scientists found that by supplying mice with bacteria associated with good patient outcomes, they could make mice respond to checkpoint inhibitors, even if they originally had microbiomes that were associated with non-responding human patients. This was done through fecal microbiota transplants (FMT), to colonize mice with a full microbiome that mirrors human patients, or through supplementing mice with single species or genera of bacteria, or a combination of the two. The findings were clear; the manipulation of the microbiome could shift how well mice with a variety of cancers responded to therapies, following trends these scientists saw in human patients. This was true in lung cancer, colon cancer, kidney cancer, and even skin cancer. The microbial communities in other regions of the body, such as the mouth, did not impact these cancers; it was only the gut that played a role. This was particularly puzzling as these drugs were not given orally; they should not interact with the digestive system. What, exactly, was causing changes in the gut to impact cancer cell growth in the skin? Scientists still aren’t sure, but one group found that immune cells were enriched in the gut of mice with that modeled human patients that responded to immunotherapy, potentially indicating immune activation.

While the interactions between the gut and the immune system in fighting cancer are currently unclear, and there is no single, magical bacteria associated with a better anti-cancer response, this new area of research could be groundbreaking for patients. Microbial manipulation through FMT is gaining popularity as a way to treat severe microbial infections, and could be expanded to patient care if these trends continue to be validated in cancer patients and FMT gains wider approval. In the meantime, the current research does support that a diverse microbiome results in a healthy gut and, potentially, better cancer outcomes. While your gut bacteria alone cannot cure you, a healthy, diverse diet high in fiber can give you a leg up.

Author’s note: This blog post is rather heavy on microbiology for a cancer research blog, but the author believes that science is growing ever more interdisciplinary, and that understanding cancer relies on understanding the systems within and around us.

Works discussed:

  • Matson, V., Fessler, J., Bao, R., Chongsuwat, T., Zha, Y., Alegre, M. L., … & Gajewski, T. F. (2018). The commensal microbiome is associated with anti–PD-1 efficacy in metastatic melanoma patients. Science, 359(6371), 104-108. DOI: 10.1126/science.aao3290
  • Gopalakrishnan, V., Spencer, C. N., Nezi, L., Reuben, A., Andrews, M. C., Karpinets, T. V., … & Cogdill, A. P. (2018). Gut microbiome modulates response to anti–PD-1 immunotherapy in melanoma patients. Science, 359(6371), 97-103. DOI: 10.1126/science.aan4236
  • Routy, B., Le Chatelier, E., Derosa, L., Duong, C. P., Alou, M. T., Daillère, R., … & Fidelle, M. (2018). Gut microbiome influences efficacy of PD-1–based immunotherapy against epithelial tumors. Science, 359(6371), 91-97. DOI: 10.1126/science.aan3706

Image source: NIH Image Gallery