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Could cancer immunotherapy success depend on gut bacteria?

Gut bacteria can penetrate tumor cells and boost the effectiveness of an experimental immunotherapy that targets the CD47 protein.

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Photo by National Cancer Institute from Unsplash.com

Could the response to cancer immunotherapy depend on bacteria that originate in the gut and travel to the tumor?

A study by researchers at UT Southwestern Medical Center and the University of Chicago suggests exactly that, revealing that gut bacteria can penetrate tumor cells and boost the effectiveness of an experimental immunotherapy that targets the CD47 protein.

Using mouse models of malignancy, the scientists found that the intestinal microbe Bifidobacterium accumulates within tumors, transforming anti-CD47 unresponsive tumors into responsive ones.

The team’s study, published today in the Journal of Experimental Medicine, discovered that the response to treatment depends on the type of bacteria living in the animals’ guts. They then identified the mechanism, finding that the combination of antibodies against CD47 and gut bacteria works via the body’s STING pathway of innate immunity – the body’s first line of defense against infection.

Their experiments used mice from different resource facilities, antibiotic-fed mice, and mice raised in a germ-free environment.

In one experiment, they studied mice raised in two different facilities and that had distinct mixtures of bacteria in their intestines. One group was responsive to anti-CD47 and another was not. The second group became responsive, however, after being housed with the responders, indicating that oral transfer or contact transmission of gut bacteria occurred between groups, the researchers say.

The protein CD47 is expressed in high levels on the surface of many cancer cells, where it acts as a “don’t eat me” signal to the immune system’s macrophages, commonly known as white blood cells. As a result, anti-CD47, also known as CD47 blockade therapy, is currently under investigation in multiple clinical trials. However, the mouse studies that predated those trials had mixed results, with only some mice responding to the anti-CD47 therapy, explains corresponding author Yang-Xin Fu, M.D., Ph.D., professor of pathology, immunology, and radiation at UT Southwestern.

“We felt we needed to improve anti-CD47 therapy and understand the mechanisms,” he says, leading them to wonder about the gut microbiome, the bacteria that grow in the intestines and aid with digestion. That bacterial ecosystem, sometimes called the microbiota, is also known to affect the gut’s ability to resist pathogens and the host’s response to cancer immunotherapy.

“But how the microbiota does that has been unclear,” Fu says. “This study finds that some of the bacteria from the gut travel to the tumor and get into the cells, or microenvironment, where the bacteria facilitate CD47 blockade’s ability to attack the tumor. We found it does that via the immune signaling pathway called stimulator of interferon genes (STING).”

The findings suggest that a probiotic might someday be used to improve anti-CD47 therapy, says Fu, a Cancer Prevention and Research Institute (CPRIT) Scholar and holder of the Mary Nell and Ralph B. Rogers Professorship in Immunology at UT Southwestern.

The researchers also found that tumor-bearing mice that normally respond to anti-CD47 treatment failed to respond if their gut bacteria were killed off by antibiotics. In contrast, anti-CD47 treatment became effective in mice that are usually nonresponsive when these animals were supplemented with Bifidobacteria, a type of bacteria that is often found in the gastrointestinal tract of healthy mice and humans.

They further discovered that the bacteria migrate into tumors, activating the STING immune signaling pathway. This sets off production of immune signaling molecules such as type 1 interferons and activating immune cells that appear to attack and destroy the tumor once the anti-CD47 agent nullifies the CD47’s “don’t eat me” tag, the researchers report. The researchers found that mice genetically unable to activate type 1 interferon failed to respond to the bacteria-immunotherapy approach. Similarly, mice unable to access the STING pathway showed no benefit from the combined bacteria-immunotherapy approach, confirming that STING signaling is essential.

“It is very possible that more than one type of gut microbiota could enhance tumor immunity in a similar way and we would like to investigate that,” he adds.

Fu and Ralph R. Weichselbaum, M.D., at the University of Chicago led the study. Co-authors include lead authors Yaoyao Shi and Wenxin Zheng as well as Kaiting Yang, Katharine G. Harris, Kaiyuan Ni, Lai Xue, Wenbin Lin, and Eugene B. Chang, all of the University of Chicago.

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Fitness

Treatment options to help overcome knee pain for sports enthusiasts

“Sports-related pain should be evaluated quickly, especially when it’s difficult to put weight on the knee, swelling occurs or there is restricted range of motion,” said Dr. Alexander Meininger, orthopedic surgeon and MACI consultant.

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Millions of people experience chronic pain, with knee pain among the most common. Athletes and active adults know the impact activities like running and skiing can have on their knees, but when chronic knee pain makes it difficult to do those activities, or even day-to-day tasks like walking up the stairs, people may often face challenges.

According to the journal “Cartilage,” unlike other tissues, cartilage does not repair itself and, without proper treatment, can worsen over time and become more difficult to treat. However, options like FDA-approved knee cartilage repair surgery MACI (autologous cultured chondrocytes on porcine collagen membrane) uses a patient’s cells to help repair cartilage defects and may help alleviate knee pain.

“Sports-related pain should be evaluated quickly, especially when it’s difficult to put weight on the knee, swelling occurs or there is restricted range of motion,” said Dr. Alexander Meininger, orthopedic surgeon and MACI consultant.

Justin Keys, a former patient of Meininger and avid skier, knows that the long-term outcomes of knee cartilage surgery can be worth the short-term sacrifices. After several injuries, including an ACL injury, Keys struggled with most activities except walking on flat, paved surfaces. After consulting with Meininger, Keys chose knee cartilage repair to help get back to his active lifestyle.

Keys considered whether to manage the injury as-is or choose MACI and undergo rehabilitation to potentially get back to his favorite activities in the future. He knew he could no longer use short-term relief methods and had to address his pain with a treatment to help provide lasting relief.

For athletes like Keys who want to fix knee pain, it’s important to consider these steps:

Discuss Options with Your Doctor

Patients should talk to their doctors and undergo an MRI to help assess the internal structures of the knee. Meininger recommends patients and their doctors discuss options for long-term knee restoration health, preserving function for future decades and recognizing the short-term sacrifice.

Set Yourself Up for Success

Experts like Meininger suggest patients take steps ahead of surgery to help their recovery.

“The important thing is to be as fit as possible and use the preseason months to undergo surgery and rehab,” Meininger said.

Patients can take steps to prep their home for recovery, which may include:

  • Bringing necessities down from hard-to-reach shelves
  • Moving furniture to ensure clear pathways
  • Installing shower safety handles to minimize potential falls

The Road to Rehab and Recovery

Rehabilitation takes time and everyone’s experience is unique. It can be as much of a mental challenge as it is physical. Committing to a physical therapy regime, staying hydrated and eating well are important aspects to support recovery. Patients should talk to their doctors with questions and before starting any exercises.

IMPORTANT SAFETY INFORMATION

Do not use if you are allergic to antibiotics such as gentamicin or materials from cow or pig; have severe osteoarthritis of the knee, other severe inflammatory conditions, infections or inflammation in the bone joint and other surrounding tissue or blood clotting conditions; had knee surgery in the past 6 months, not including surgery for obtaining a cartilage biopsy or a surgical procedure to prepare your knee for a MACI implant; or cannot follow a rehabilitation program post-surgery.

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Fitness

6 Exercise safety tips

Now, as social restrictions ease, you may find yourself stepping up your workouts, whether you’re training for an event or working to improve your game in a recreational league.

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In the wake of the COVID-19 pandemic, many Americans are more aware of their health and wellness. Now, as social restrictions ease, you may find yourself stepping up your workouts, whether you’re training for an event or working to improve your game in a recreational league.

Sprains, strains and injuries can happen to even the most seasoned athletes. When you’re testing your limits, even a minor injury can alter your performance. Consider products and supports like these from the CURAD Performance Series product line, available at Walmart and Amazon, to help you get back in the game quickly and safely.

Find more resources to support your fitness journey at CURAD.com.

Keep Dirt and Germs Away

The more active you are, the harder it can be to find a bandage that stays with you all day or all game long.

Spray Away Sore Spots

Controlling mild pain can help keep you at the top of your game, and a topical analgesic works fast to heal common pain brought on by fitness and exercise, such as pain in knees, feet, shoulders and backs.

Put Pain in the Past

When recovery becomes the name of the game and pain relief is needed after daily workouts or bodily injuries. Cold packs work to heal bruises, reduce swelling and relieve headaches and general pain points while microwavable heat packs provide satisfying heat therapy to address sore and stiff joints, muscle cramps and tension.

Reduce Impact of Knee Strain

Weak, injured or arthritic knees can come from many sources, including tendonitis and a wide range of conditions that result in strain or overuse. An adjustable band can provide support for on-field sports and during workouts or everyday activities.

Manage Pain and Relieve Pressure

If you participate in endurance and strength exercises or certain sports, you may ask a lot of your joints. Kinesiology tape can be configured a multitude of ways to help reduce pain and improve blood circulation, as well as relieve tension and pressure.

Control Back Strain

When your back is strained, your body and performance can suffer. A mild or moderate sprain can benefit from strong support and compression.

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Fitness

Exercise can provide relief for dry, itchy eyes

A significant increase in tear secretion and tear film stability after participating in aerobic exercise can be another remedy for relieving dry, itchy eyes.

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Photo by Quinten de Graaf from Unsplash.com

A team led by researchers from the University of Waterloo discovered that a significant increase in tear secretion and tear film stability after participating in aerobic exercise can be another remedy for relieving dry, itchy eyes. 

Every time we blink, our eyes are covered in tear film—an essential protective coating necessary for maintaining healthy ocular function. Healthy tear film comprises three layers–oil, water, and mucin–that work together to hydrate the ocular surface and protect against infection-causing irritants like dust or dirt.

When any part of the tear film becomes unstable, the ocular surface can develop dry spots, causing eye symptoms like itchiness or stinging and burning sensations.

“With so much of our activity tied to screen usage, dry eye symptoms are becoming increasingly common,” said Heinz Otchere, a PhD candidate in vision science at Waterloo. “Instead of having to use eye drops or other alternative treatments, our study aimed to determine if remaining physically active can be an effective preventative measure against dryness.”

Fifty-two participants were divided into two groups—athlete and non-athlete—to participate in an exercise session. Participants in the athlete group exercised at least five times per week, while non-athlete participants exercised no more than once per week. Researchers, which included experts from the University of Cape Coast in Ghana, performed visual examinations before and five minutes after each exercise session, where tear secretion and tear break-up time were assessed.

While participants in the athlete group showed the largest increase, Otchere says all participants experienced a meaningful boost in tear quantity and tear film stability after the exercise session. 

“It can be challenging for people to regularly exercise when the demand is there to work increasingly longer hours in front of screens,” Otchere said. “However, our findings show physical activity can be really important for not just our overall well-being, but for our ocular health too.”

The study, Differential effect of maximal incremental treadmill exercise on tear secretion and tear film stability in athletes and non-athletes, was co-authored by Otchere, the University of Cape Coast’s Samuel Abokyi, Sekyere Nyamaah, and Michael Ntodie, and Ghana’s Our Lady of Grace Hospital’s Yaw Osei Akoto. It was recently published in the Experimental Eye Research journal.

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