What Are Neutrophil Extracellular Traps (NETs)? How Immune "Spider Webs" Fuel Cancer & New Treatments (2025 Guide)

If you or a loved one are navigating cancer, you’ve likely heard a lot about "tumors," "genes," and "mutations." But a groundbreaking new scientific review is shining a spotlight on a completely different player in the cancer story: a part of your own immune system called the Neutrophil.

For years, scientists viewed neutrophils as simple foot soldiers—the first responders that rush to a cut or infection to fight off bacteria. But new research reveals that in the context of cancer, these soldiers can be tricked into becoming double agents. They produce sticky, web-like structures called NETs (Neutrophil Extracellular Traps). While meant to catch bacteria, these nets can accidentally catch cancer cells, shielding them from treatment and helping them spread.

This might sound scary, but it’s actually good news. Why? Because by understanding this hidden mechanism, researchers are developing entirely new ways to stop it. This article explains these complex findings in plain English to help you understand what’s happening in the body and why there is new hope on the horizon.

Understanding the Players: The Tumor and the Soldiers

Before diving into the "webs," it helps to understand the battlefield.

It’s Not Just a Lump: The "TIME"

We often think of a tumor as just a ball of cancer cells. But scientists now know it’s more like a rogue organ or a complex city. This city has its own blood vessels, structural support, and—crucially—immune cells that have moved in. Scientists call this the Tumor Immune Microenvironment (TIME). Everything that happens to a cancer patient, from treatment to stress, affects not just the cancer cells, but this entire "city" around them.

Meet the Neutrophil

Neutrophils are the most abundant white blood cells in your body, making up 50% to 70% of your immune system's frontline forces. They are the "first responders" to any injury or infection. If you get a cut, neutrophils are the first on the scene to eat bacteria and clean up debris. Because there are so many of them, their behavior has a massive impact on your health.

The Discovery of NETs

For decades, we thought neutrophils only had two modes: eat bacteria or release toxic chemicals to kill them. It wasn't until 2004 that scientists discovered a third, dramatic mode: NETosis. This is the process where a neutrophil effectively "explodes" on purpose. It dissolves its own internal skeleton and shoots out its DNA like a spider casting a web. While this was a revolutionary discovery for fighting infections, we are only now fully understanding how cancer hijacks this exact process for its own gain.

What Are These "Nets"?

Imagine a soldier carrying a net to catch enemy spies. That’s essentially what a neutrophil does. When it senses a threat (like bacteria), it can explode, shooting out a web made of its own DNA and sticky proteins. This web is called a NET.

In a healthy person, this is a brilliant defense strategy. The web traps bacteria so they can be destroyed.

But cancer is a master manipulator. It sends out chemical signals that trick neutrophils into shooting these nets even when there is no infection. Instead of catching bacteria, these sticky webs:

Shield the tumor: They form a physical barrier around cancer cells, protecting them from the "good" immune cells (T-cells) that try to kill them.

Act like a highway: They make the tissue slippery and easier for cancer cells to move through.

Wake up sleeping cells: They can reactivate dormant cancer cells that have been quiet for years.

The 3 Ways NETs Help Cancer Survive

The review paper details three critical ways these nets drive cancer progression. Understanding this helps explain why cancer can sometimes be so difficult to treat.

1. The "Bodyguard" Effect (Immune Evasion)

One of the most frustrating problems in cancer treatment is when the immune system knows the cancer is there but can’t reach it. NETs are partly to blame. They wrap around the tumor like a coat of armor. When your body’s hunter cells (T-cells and Natural Killer cells) arrive to destroy the tumor, they get stuck in the web and can’t get through. This is a major reason why some modern treatments, like Immunotherapy, might fail—the medicine works, but the immune cells it boosts are physically blocked from doing their job.

2. The "Spider Web" Effect (Metastasis)

For cancer to spread (metastasize), a cell has to leave the main tumor, travel through the blood, and survive in a new organ. This is a dangerous journey, and most cancer cells die along the way. NETs change the odds.

In the blood: NETs float in the bloodstream and catch circulating cancer cells like a spider catching a fly. Instead of eating them, the NETs protect them, helping them survive the journey.

At the destination: Before cancer even arrives at a new organ (like the liver or lungs), NETs can accumulate there, preparing a "nest" (scientists call this a pre-metastatic niche). This makes the new organ friendly soil for the cancer seed to grow.

The diagram above illustrates these two dangerous roles: On the left, NETs form a dense barrier around the primary tumor, physically blocking "good" immune cells (T-Cells) from entering and attacking. On the right, inside a blood vessel, a NET acts like a sticky web, catching a traveling cancer cell that might otherwise have died in the bloodstream, allowing it to survive and spread.

3. The "Awakening" (Recurrence)

Sometimes, cancer treatment works, but a few cells hide away in a "sleeping" (dormant) state. Years later, they can wake up. The paper explains that inflammation—triggered by things like smoking or infection—causes neutrophils to release NETs. These NETs contain enzymes that cut through the tissue holding the sleeping cells in place, effectively hitting the "snooze" button and waking them up to grow again.

As shown in this flowchart, your lifestyle choices (like managing stress or avoiding smoke) can intervene at the very first step. By reducing the "Triggers," you reduce the number of neutrophils that explode into NETs, thereby lowering the risk of waking up these dormant cells.

The Treatment Paradox: A Double-Edged Sword

One of the most important sections of this review discusses a difficult paradox: Standard cancer treatments can sometimes trigger NETs.

Chemotherapy & Radiation: While these kill cancer cells, they also cause stress and damage that can trigger neutrophils to release more nets.

Surgery: The physical stress of surgery is necessary to remove a tumor, but the body responds to the "wound" by sending neutrophils, which release nets.

Important Note: This does not mean you should avoid these life-saving treatments. They are still your best defense. Instead, this knowledge is guiding doctors to test new combinations. For example, giving a "NET-blocking" drug alongside chemotherapy might prevent the bad side effects while letting the chemo do its job.

What You Can Control: The Lifestyle Link

Perhaps the most empowering part of this research is the link between your lifestyle and your neutrophils. The paper highlights several "modifiable risk factors" that influence how many NETs your body produces.

1. Stress Management is Biological, Not Just Psychological

We often hear "reduce stress" as vague advice. This paper gives us the hard science. Chronic stress releases hormones (glucocorticoids) that directly tell neutrophils to release more nets. This suggests that practices like meditation, therapy, or deep breathing aren't just for your mind—they are physically lowering the "web count" in your body, potentially making it harder for cancer to spread.

2. The Importance of Sleep (Circadian Rhythms)

Your immune system has a clock. The paper reveals that neutrophils are more active and prone to making nets at certain times of the day (usually when you are resting). Disrupted sleep or erratic schedules can throw this rhythm off, keeping your neutrophils in a high-alert, net-producing state. Prioritizing regular, quality sleep is a tangible way to help regulate your immune system.

3. Smoking and Inflammation

Smoking is a massive trigger for inflammation. The paper details how tobacco smoke specifically triggers NETs that can "wake up" dormant cancer cells. Stopping smoking does more than protect your lungs; it calms down the neutrophil response throughout your whole body.

The Future: New Tests and "Scissors" for the Webs

The review concludes with hope. Now that scientists know about NETs, they are building tools to fight them:

New Blood Tests: Researchers have found a specific marker (called H3Clip) that lets them measure how many NETs are in your blood. In the future, a simple blood test could tell doctors if your "NET level" is high, helping them decide on the best treatment.

"Scissors" for the Webs (DNase): Since NETs are made of DNA, scientists are testing drugs containing an enzyme called DNase. Think of DNase as molecular scissors. It chops up the DNA webs, destroying the shield around the tumor and clearing the "nests" in distant organs.

Blocking the Signal: New drugs are being tested that block the chemical signals (like IL-8) that tell neutrophils to release the nets in the first place.

The Bottom Line

This research represents a massive shift in how we understand cancer. It’s not just about the tumor cells anymore; it’s about the environment they live in. Neutrophil Extracellular Traps (NETs) are a key part of that environment.

By discovering that these "spider webs" exist, science has exposed a major hiding spot for cancer. And with new trials underway testing NET-destroying drugs, we are moving toward a future where we don't just poison the tumor—we dismantle its defenses, leaving it nowhere to hide.

This article is based on the article: Shahzad, M.H., Rayes, R.F., Cools-Lartigue, J. et al. Neutrophil extracellular traps in cancer. Nat Rev Cancer (2025). https://doi.org/10.1038/s41568-025-00888-7