NF1 Associated with More Cancer Types Than Previously Known
'Artificial Lymph Node' Shows Potential To Treat Cancer
Johns Hopkins Medicine scientists say they have developed an artificial lymph node with the potential to treat cancer, according to a new study in mice and human cells. The newly developed lymph node -; a sac filled with immune system components -; is implanted under the skin, and is designed to act like a learning hub and stimulator to teach immune system T-cells to recognize and kill cancer cells.
Details of the experiments are published recently online and in the June 6 issue of Advanced Materials.
Lymph nodes -; tiny glands throughout the body, mainly in the neck, armpits and groin -; are part of the immune systems of mammals, including mice and people. They number in the hundreds so that immune cells in one area of the body don't have to travel far to alert the immune system to impending danger.
They are a landing spot where T-cells, the immune system's fighting cells, lay dormant, waiting to be activated to fight infections or other abnormal cells. Because cancers can trick T-cells into staying dormant, the artificial lymph node was designed to inform and activate T-cells that are injected alongside the lymph node."
Natalie Livingston, Ph.D., first author of the research and currently a postdoctoral researcher at Massachusetts General Hospital
To create the artificial lymph node, the scientists used hyaluronic acid, a moisturizing substance commonly used in cosmetics and lotions and found naturally in the body's skin and joints.
Because of its properties, hyaluronic acid is often used in biodegradable materials such as wound healing patches meant to be implanted or applied to the body. Among those properties, hyaluronic acid can connect with T-cells via a cell surface receptor.
Johns Hopkins scientists led by Jonathan Schneck, M.D., Ph.D., published research in 2019 showing that hyaluronic acid boosts T-cell activation.
For the current study, the Johns Hopkins team used hyaluronic acid as the scaffolding, or base, for their new lymph node, and added MHC (major histocompatibility complex) or HLA (human histocompatibility antigen) molecules, which rev up T-cells and other immune system components. Then, they also added molecules and antigens common to cancer cells to "teach" T-cells what to look for.
"By adding different antibodies to the artificial lymph node, we have the ability to control what the T-cells are being activated to search for," says Livingston.
The resulting artificial lymph node is about 150 microns in size, about twice the width of a human hair. It's small enough to remain under the skin and large enough to avoid being swept away in the blood stream.
"An advantage to this approach over other cell-based therapies such as CAR-T is fewer manufacturing steps," says Schneck, who is a professor of pathology, medicine and oncology at the Johns Hopkins University School of Medicine, director of the Johns Hopkins Center for Translational Immunoengineering, and a member of the Institute for Cell Engineering, Kimmel Cancer Center and Institute for Nanobiotechnology.
Current cell-based therapies require extracting T-cells from a patient, manipulating them outside of the body to recognize a particular type of cancer, and injecting them back into the patient. "In our approach, we inject T-cells along with an artificial lymph node, and the T-cells get primed and educated by the artificial lymph node inside of the body. Then, the T-cells can travel anywhere to destroy cancer cells," says Schneck, who led the research team, along with Hai-Quan Mao, Ph.D., director of Johns Hopkins' Nanobiotechnology Institute.
Livingston, Schneck and the research team tested the artificial lymph node in mice that were implanted with either melanoma or colon cancers. Six days after the tumors were implanted, the mice received injections of the artificial lymph node and T-cells.
The Johns Hopkins team compared these mice with ones receiving the artificial lymph node alone, those receiving T-cells alone (which have not been activated by the artificial lymph node) and those receiving T-cells in combination with a class of immunotherapy drug called anti-PD-1.
Nine days later, mice with melanomas and colon cancers that received a combination of the artificial lymph node, T-cells and the anti-PD-1 drug had the best survival rates (three of the seven mice were still alive at 33 days), compared with other groups that only lived to about 26 days. This group of mice also had the slowest cancer growth rate. It took between five and 10 days longer for their cancers to double in size than the other groups.
The scientists also found that the artificial lymph node attracted an influx of other immune cells and acts as an "immunologically active niche" to help to further stimulate the immune system. When T-cells were injected into the mice alongside the artificial lymph node, T-cell numbers grew as much as nine times more plentiful.
Livingston says the artificial lymph node approach is different from a cancer vaccine, which typically activates a dendritic cell, an immune system component that teaches T-cells what to search for. People with cancer often develop malfunctioning dendritic cells, and the artificial lymph node skips the dendritic cell to directly activate T-cells.
The research team plans to conduct additional laboratory studies to add more immune signaling molecules to the lymph node and recruit more of the host's immune cells to the artificial lymph node environment.
"We blended the disciplines of materials science and immunology to create a potential therapy that forms its own immunology community -; a kind of living drug," says Schneck.
The researchers have filed for a patent involving the technology described in their research.
Funding for the research was provided by the National Institutes of Health (R01EB029341, R21CA185819, P41EB028239, T32AI007417), the National Science Foundation, the Ruth L. Kirschstein Predoctoral Individual National Research Service Award (F31CA275271), the NIH Cancer Nanotechnology Training Center at the Johns Hopkins Institute for NanoBioTechnology, the National Science Foundation Graduate Research Fellowship, the ARCS Foundation, the Siebel Foundation, and the Natural Sciences and Engineering Research Council of Canada's Postgraduate Scholarships – Doctoral Award.
Other Johns Hopkins researchers who contributed to the study are John Hickey, Hajin Sim, Sebastian Salathe, Joseph Choy, Jiayuan Kong, Aliyah Silver, Jessica Stelzel, Mary Omotoso, Shuyi Li, Worarat Chaisawangwong, Sayantika Roy, Emily Ariail, Mara Lanis, Pratibha Pradeep, Joan Glick Bieler, Savannah Est Witte, Elissa Leonard, Joshua Doloff and Jamie Spangler.
Source:
Journal reference:
Livingston, N. K., et al. (2024). In Vivo Stimulation of Therapeutic Antigen‐Specific T Cells in an Artificial Lymph Node Matrix. Advanced Materials. Doi.Org/10.1002/adma.202310043.
When Do Swollen Lymph Nodes Mean Cancer?
Swollen lymph nodes, or what doctors call lymphadenopathy, are often caused by infections or a condition that affects your immune system. They usually clear up as your body heals.
But sometimes, cancer cells may travel through your bloodstream and end up in your lymph nodes, or even start there.
Your doctor can help you figure out what's causing your lymph nodes to feel sore and larger than usual.
Lymph nodes aren't just in your neck. You have hundreds of them throughout your body as they work to keep you healthy. (Photo Credit: iStock/Getty Images)
Your lymphatic system is a key part of your immune system. It's made up of organs, blood vessels, and tissues that help you stay healthy. It includes your:
More than 600 small, kidney bean-shaped lymph nodes are clustered throughout your body -- under your neck, in your armpits and groin, and in the middle of your chest and belly. They store immune cells and act as filters to remove germs, dead and damaged cells, and other waste from your body.
Swollen lymph nodes are a sign that they're working hard. More immune cells may be going there, and more waste could be building up. Swelling usually signals an infection of some kind, but it could also be from severe allergies, ongoing stress, conditions such as rheumatoid arthritis or lupus, or rarely, cancer.
Often, swollen lymph nodes will be close to where the issue is. For instance, when you have strep throat, lymph nodes in your neck may swell. Shingles will cause swollen lymph nodes in the area where the rash breaks out. People who have breast cancer may get swollen lymph nodes in their armpit.
When two or more areas of your lymph nodes are swollen, an issue is affecting your entire body. The medical term for this is generalized lymphadenopathy.
It can happen for a range of reasons, from chickenpox and HIV to a type of cancer.
Your glands are more likely to swell if:
If cancer is the cause of your swollen glands, it's usually because cancer cells have spread there from another place in your body. This is called metastasis. Once a tumor forms in your body, cancer cells can break loose from it and travel to different organs through your bloodstream or your lymph system.
Usually, you should be able to gently move swollen glands under your skin. They'll feel soft and could be tender or slightly painful to the touch.
Cancerous lymph nodes
There's no way to tell if a swollen gland is a sign of cancer just by how it feels.
You'll often have a good idea why a lymph node is swollen -- for instance, you've got a cold, or your tooth is infected, or you have a cut that isn't healing well. But If you can't come up with a reason, it may be time to get checked out.
You'll also want to make an appointment if your glands:
Your doctor should also know if you have any of these symptoms:
Swollen lymph nodes close to your collarbone or the lower part of your neck are more likely to be cancer. On the right side, they're linked to your lungs and esophagus , while on the left, they relate to organs in your belly. Swollen lymph nodes in your armpit when you don't have a rash or close to your elbow can also raise concern.
But keep in mind that many other health issues besides cancer can cause your glands to look or feel different. There's no way of knowing the cause until you see a doctor and tests are done.
Because cancer is rarely the cause of swollen glands, your doctor will probably try to rule out more common reasons first. They'll do a physical exam and ask you about recent events, such as if you've:
They'll want to know what medications you're taking and other symptoms you have.
Tests your doctor may order
Your doctor will probably do a complete blood count (CBC) to get a picture of your general health as well as more detailed information about your white blood cells, which fight infection. Depending on your other symptoms and your medical history, they may want additional blood tests or X-rays, too.
For instance, if you have swollen lymph nodes throughout your body, your doctor may ask for a CBC, a chest X-ray, and an HIV test. If those results are normal, you might get other tests, perhaps for tuberculosis or syphilis, an antinuclear antibody test (which checks your immune system), or a heterophile test (which looks for the Epstein-Barr virus).
If these tests don't show another cause and your glands don't go back to normal in 3-4 weeks, your doctor will likely do a biopsy. Using a very thin needle, they'll take a sample of cells from one of your glands and send it to a lab for a better look. Since the swelling may go away or another cause could be found while you're waiting to do a biopsy, this time lag prevents you from getting procedures you don't need.
Tests that check for cancer
If your doctor thinks your swollen lymph nodes could be cancer, tests and imaging can confirm the diagnosis or point to something else. Based on where the cancer might be, you could get a chest X-ray, an ultrasound, a CT scan, or an MRI. A scan called FDG-PET, which stands for fluorodeoxyglucose with positron emission tomography, can help find lymphoma and other cancers.
You'll probably get a procedure called a lymph node dissection or lymphadenectomy. Cells from one or more of your nodes are removed. It's a minor surgery that lasts about an hour. You'll be given anesthesia that allows you to sleep through it.
The sample cells from your lymph node then get sent to a lab so a specialist can check them with a microscope for cancer.
Cancer in your lymph nodes is often a cancer that has spread from another place in your body. Rarely, the cancer begins in your lymph nodes. Lymphoma is a broad term that includes any cancer of your lymph system.
Some types include:
If cancer is found in one of your lymph nodes, more tests and procedures are usually done. The more information your doctor has about your cancer, including the size of the tumor, where it is in your body, and how much it's spread, the more accurate they can be when talking about your outlook and treatment options.
How cancer is staged
Doctors often use a type of system to help stage, or describe, your cancer and decide the next steps to take. One that's often used is called the tumor-nodes-metastasis (TNM) staging system.
Generally speaking, it provides details about the:
Based on that data, your doctor can then assign a stage to your cancer.
Stage I. Smaller tumors that haven't spread to nearby lymph nodes or other areas.
Stage II. Larger tumors that haven't spread anywhere else.
Stage III. Large tumors that have spread to lymph nodes.
Stage IV. Cancer that has spread from the original tumor to other body parts.
Staging may not be used if you have leukemia.
Based on the source of the cancer cells and how far away it is from your swollen glands, your doctor will suggest a treatment plan. It could include surgery, radiation, chemotherapy, or a combination of treatments.
Once cancer cells have entered your lymph nodes, they're more likely to come back after treatment. Removing all the lymph nodes that were affected can help stop this from happening.
Your doctor will decide the best time to remove any lymph nodes that contain cancer cells. You could have this procedure after another cancer therapy, such as radiation or chemotherapy. Or your doctor may do it right away. It may be a standalone lymphadenectomy, similar to what you had before when you were first diagnosed. Or it could be part of a larger surgery to remove a tumor.
Most of the time, it's a minor outpatient procedure, meaning that you can go home the same day and don't have to stay overnight in a hospital. Any pain you feel should be mild and able to be managed with over-the-counter medications. But some complications are possible. They include:
Nerve damage. If the nerves around the gland were removed during the surgery, that area may feel numb or stiff.
Fibrosis. Thick scar tissue could build up over the site, making it harder for you to move that body part.
Lymphedema.Lymph is the fluid that travels through your lymphatic system. If it stops flowing properly and gets backed up somewhere in your body, it's a condition called lymphedema. This can happen after you've had lymph nodes removed.
If you notice swelling in the area, talk to your doctor. If the buildup is small and you caught it early, home care may help. For instance, your doctor may give you special exercises to do, since moving around can help flush the excess fluid. Or they could give you a compression garment to wear to keep more lymph from pooling in the area.
Swollen glands are a sign that your immune system is fighting off an infection or illness. They're usually not a sign of cancer. But if they don't clear up quickly or you have other symptoms, see your doctor so they can run tests and find the cause.
How do you relieve swollen lymph nodes?
If your glands are sore, you can try:
While none of these tips will bring your glands back down to normal size, they will help make you more comfortable until they shrink on their own.
How long does a swollen lymph node take to go away?
Once your infection or illness clears up, the swelling in your glands should, too.
What Causes Swollen Lymph Nodes In The Armpit?
The lymph nodes are small glands that are part of your immune system. They contain white blood cells and are responsible for filtering out harmful substances in the lymph fluid. Swollen lymph nodes (medically known as lymphadenopathy) can happen for several reasons. Infections, health conditions, and certain medications can all cause this reaction.
Fortunately, many causes of swollen lymph nodes are treatable. Several infections can be treated with antibiotics, antivirals, or antifungals. Chronic health conditions like an autoimmune disorder or cancer are also treatable with medications or surgery. If your lymph nodes are swollen, meet with your healthcare provider to develop a treatment plan.
When bacteria enter the body, they can cause a bacterial infection. When the lymph nodes detect harmful substances like bacteria, they react and become swollen. Several bacterial infections may be causing your symptoms, including the ones below. Cellulitis Cellulitis is the most common bacterial skin infection and occurs when bacteria like group A Streptococcus enter deeper layers of skin. This infection can cause your skin to look red, swollen, and pitted (like the peel of an orange). Other symptoms include swollen lymph nodes, a fever, and chills. Antibiotics can help improve symptoms. You can lower your risk of cellulitis by washing your hands often and keeping wounds clean, dry, and covered. Cat Scratch Disease Cat scratch disease is a bacterial infection spread by cats that can occur when an infected cat licks a person's open wound or bites or scratches to break the skin. This infection causes discolored or swollen skin, raised sores (lesions) that may contain pus, swollen lymph nodes, headaches, a fever, poor appetite, and fatigue. The lymph nodes closest to the scratch may feel painful, tender, and swollen. The cause of cat scratch disease is a type of bacteria called Bartonella henselae. Up to 30% of cats carry this type of bacteria, and infected cats often have no symptoms. To lower your risk of cat scratch disease, never let your cat lick an open wound. If you experience a cat bite or scratch, wash the area with soap and water immediately. Lyme Disease Lyme disease is a bacterial infection caused by the bacterium Borrelia burgdorferi, which spreads from an infected tick bite. People who live near the Northeast, Mid-Atlantic, Upper Midwest, and Pacific coast are at a higher risk of being exposed to infected ticks. Common symptoms of Lyme disease include rash, fever, headache, swollen lymph nodes, and fatigue. When left untreated, Lyme disease may lead to heart, joint, and nervous system symptoms. These symptoms often start 3-30 days after a tick bite. Trichomycosis Trichomycosis is a bacterial infection of the underarm hairs, which causes irritation and discomfort in the armpit. Common symptoms of trichomycosis often include more sweat and a foul odor in the armpit. You may also notice that your sweat is yellow, red, or black. The underarm hair usually becomes thicker and more coarse as well. Trichomycosis is not contagious and can be treated with antibiotics and good hygiene. Syphilis Syphilis is a sexually transmitted infection (STI) caused by the bacterium Treponema pallidum. Symptoms of syphilis occur in stages. The first stage may cause sores or bumps on the penis, vagina, anus, rectum, lips, or mouth. As syphilis progresses, it may lead to swollen lymph nodes. Syphilis is curable with antibiotics. Toxoplasmosis Toxoplasmosis is an infection caused by Toxoplasma gondii, which can spread by consuming undercooked, contaminated meat and shellfish. You might also develop this infection by drinking contaminated water and coming into contact with cat feces. Most people exposed to toxoplasmosis do not develop symptoms because the immune system fights the infection. If you experience symptoms, you may have swollen lymph nodes and flu-like symptoms. Early treatment is necessary. A severe infection can lead to permanent damage to the brain, eyes, and other organs. Like bacteria, many viruses cause swollen lymph nodes. This happens when the immune system recognizes the virus and fights the viral infection, which can cause a host of symptoms including swelling in the armpit's lymph nodes. Mononucleosis Infectious mononucleosis, commonly known as mono, is a contagious, viral infection. It typically spreads through contact with body fluids, especially saliva. This is why it is sometimes referred to as, "the kissing disease." It can also be spread by sharing cups and utensils. Common symptoms of mono include fatigue, fever, sore throat, headache, body aches, and swollen lymph nodes in the neck and armpits. Symptoms usually start about 4-6 weeks after the infection begins. Antibiotics are not effective against mono. Most people get better with home remedies (like rest and nutritious foods) within two to four weeks—but symptoms may last several weeks to months. Influenza (The Flu) Influenza is a viral respiratory illness that infects the nose, throat, and sometimes the lungs. The flu spreads through exposure to tiny droplets when a person sneezes, coughs, or talks. Symptoms usually include a fever, chills, cough, sore throat, runny nose, body aches, headache, fatigue, and swollen lymph nodes. You can lower your risk of contracting the flu by receiving an annual flu shot, washing your hands frequently, and limiting contact with people with the flu. HIV Human immunodeficiency virus (HIV) is a serious viral illness that destroys a type of white blood cell in your immune system that helps your body fight infections. HIV greatly raises the risk of serious infections and diseases and can spread through bodily fluids like semen, vaginal fluids, and blood. Symptoms of HIV may include fever, chills, rash, night sweats, sore throat, body aches, fatigue, mouth sores, and swollen lymph nodes. Symptoms usually come and go for the first few weeks of illness. When diagnosed early, you can manage HIV with antiviral medications. Shingles Shingles is a viral infection caused by the varicella-zoster virus (VZV), the same virus that causes chickenpox. If you had chickenpox as a child, you can develop shingles as an adult. About 1 in 3 people in the United States will experience shingles at some time—and the risk tends to increase with age. However, getting the shingles vaccine can reduce your risk of the infection. If you experience shingles, you may develop symptoms like pain, itchy skin, a painful and blister-like rash, fever, chills, headache, and swollen lymph nodes. Shingles is treatable with antiviral medications like Zovirax (acyclovir). Hepatitis Hepatitis refers to the inflammation of the liver. Viral hepatitis may be caused by hepatitis A, hepatitis B, or hepatitis C. Many people with hepatitis do not show signs of it—but if you do develop symptoms, they may include fever, fatigue, nausea, vomiting, loss of appetite, pain, dark urine, clay-colored stools, and swollen lymph nodes. The infection may last weeks to months, but vaccines are available to prevent hepatitis from occurring. Health conditions like autoimmune disorders and certain types of cancer may cause swollen lymph nodes in the armpits. The treatment options for these causes depend on the underlying condition you have and the severity of your symptoms. Cancer Certain types of cancer affect the lymph nodes. Hodgkin lymphoma and non-Hodgkin lymphoma are cancers that start in the lymph nodes, while leukemia affects the blood cells and may eventually cause swollen lymph nodes. Other types of cancer may start in another area of the body and spread to the lymph nodes through the lymph fluid or blood. Cancers of the head, neck, and breast are most likely to spread to the lymph nodes in the armpits because of their proximity to your armpits. It's important to seek care from a healthcare provider as soon as possible. The treatment plan for cancer depends on the type of cancer you have, how advanced it is, and the severity of your symptoms. Common treatment options for cancer typically include surgery, chemotherapy, radiation therapy, and immunotherapy. Rheumatoid Arthritis Rheumatoid arthritis (RA) is an inflammatory autoimmune condition that causes the immune system to attack healthy cells in the joints, leading to inflammation. People with RA usually experience pain in the joints of the hands, wrists, or knees. Symptoms of RA often include pain, swelling, and stiffness in the joints. You may also notice fever, fatigue, weight loss, weakness, and swollen lymph nodes. Medications can help reduce symptoms. Systemic Lupus Erythematosus Systemic lupus erythematosus, more commonly known as lupus, is a chronic autoimmune condition that occurs when the immune system attacks healthy tissues in the body. Lupus affects several organs and can cause inflammation and damage to the skin, joints, heart, lungs, kidneys, blood cells, or brain. Lupus symptoms can vary widely, including pain, fever, a rash, hair loss, sores, and swollen lymph nodes. There is no cure for lupus but medications and lifestyle changes can help you manage the condition well. Several other factors can also contribute to the swelling in your lymph nodes. They may include vaccine reactions, medications, and injuries. Vaccine Reaction In very rare cases, a vaccine could cause a reaction affecting the lymph nodes One 2022 case study found that one person who received the COVID-19 vaccine experienced swelling in the lymph node in their armpit. The risk of this reaction may increase with subsequent (additional) vaccines. In this case study, the person experienced lymph node swelling after her third COVID-19 vaccine. Medication Side Effects All medications have some side effects, but certain medications raise the risk of swelling in the lymph nodes in the armpits. These drugs include: Aloprim (allopurinol): Treats gout and kidney stones Tenormin (atenolol): Treats high blood pressure and chest pain Capoten (captopril): Treats high blood pressure and heart failure Tegretol (carbamazepine): Treats seizures and bipolar disorder Apresoline (hydralazine): Treats high blood pressure Dilantin (phenytoin): Treats seizures Mysoline (primidone): Treats seizure disorders Daraprim (pyrimethamine): Treats toxoplasmosis Cardioquin (quinidine): Treats irregular heartbeats (arrhythmias) Clinoril (sulindac): Treats pain Swollen lymph nodes can also be a side effect of certain drug classes that treat bacterial infection—such as Cephalosporins, Penicillins, and Sulfonamides. Injury Swelling in the armpit can sometimes be due to a muscle strain or injury. The muscles in and around the armpits could become sore after overusing them with lifting, pulling, throwing, or pushing motions. Injuries to the shoulder, such as a shoulder dislocation, can also lead to pain and swelling in the armpit. As the injury heals, the swelling typically goes away. Ingrown Hair Ingrown hairs in the armpits occur when your hair curls back into a shallow layer of the skin instead of growing outward. If you develop ingrown hair, you'll likely experience irritation, swelling, pain, bumps, and itching in the armpits. If your ingrown hair becomes affected, it can develop into a condition called folliculitis, which may require antibiotics or antibacterial home remedies for treatment. There are several treatment options for swollen lymph nodes in the armpits, but your exact treatment plan will depend on what's causing your swelling. If you have swollen lymph nodes, see your healthcare provider for an accurate diagnosis and begin treatment if necessary. During your appointment, your provider will perform a physical exam and ask questions about your medical history, recent symptoms, current medications, and family history. They may also order additional diagnostic tests such as blood tests, imaging studies, and lymph node biopsies. Once your provider learns the cause of your symptoms, treatment will depend on what's causing your swollen lymph nodes. Treatment options may include: Cause of Swollen Lymph Nodes Recommended Treatment Bacterial infections Antibiotics Viral infections Antiviral medications and rest Cancer Surgery, chemotherapy, radiation therapy, or immunotherapy Autoimmune disorders Immunosuppressant medications and supportive therapies Medication side effects Stopping the medication Injury or ingrown hair Self-care strategies and over-the-counter home remedies It's normal to experience swollen lymph nodes if you have an infection. As you recover, your lymph node swelling should improve. However, if your swollen lymph nodes stick around even after you're feeling better, it's a good idea to see your healthcare provider. Contact your healthcare provider urgently if you have swollen lymph nodes alongside the following symptoms: Extreme fatigue Unintended weight loss Night sweats Weakness These symptoms may be a sign of a more serious condition, so it's important to get support right away to reduce the risk of potential complications. Lymph nodes are a part of your immune system and can become swollen if you've developed an infection, condition, or injury. There are several possible causes of swelling in your lymph nodes ranging from bacterial infections, viral infections, autoimmune disorders, cancer, and medication side effects. Treatment will depend on the underlying cause of your symptoms, but medications, therapies, and home remedies can help reduce the swelling effectively. 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