Harnessing the power of lightning to revolutionize cancer immunotherapy
Explore the ScienceImagine if we could harness the power of lightning—not to destroy, but to heal. What if the same phenomenon that lights up the sky during a thunderstorm could be tamed to activate our body's defenses against cancer? This isn't science fiction; it's the cutting edge of cancer research today. Scientists are now using cold atmospheric plasma (CAP)—a mysterious, energy-rich state of matter sometimes called "the fourth state of matter"—to dramatically enhance our immune system's ability to seek and destroy cancer cells. 9
This revolutionary approach represents a paradigm shift in cancer therapy, moving beyond traditional treatments that often weaken the body toward a treatment that actively strengthens our natural defenses. The convergence of physics and biology in this field is opening unprecedented possibilities for cancer treatment that are both effective and minimally invasive.
Plasma makes up 99% of the visible universe
Plasma is often called the fourth state of matter—distinct from solids, liquids, and gases. While most of us rarely encounter plasma in our daily lives, it's actually the most abundant form of ordinary matter in the universe, constituting most of the sun and other stars. Naturally occurring plasma on Earth includes lightning and the aurora borealis. Scientists have now learned to create and control plasma at room temperature and atmospheric pressure—hence the name "cold atmospheric plasma." 9
Unlike the intensely hot plasmas found in stars, CAP can be safely applied to biological tissues without causing thermal damage. This is achieved through sophisticated engineering that creates non-equilibrium discharge conditions where electrons reach very high temperatures (thousands of degrees Kelvin) while the heavier ions and neutral particles remain near room temperature. 1
CAP is composed of a complex mixture of charged particles (electrons and ions), electric fields, ultraviolet radiation, and most importantly, reactive oxygen and nitrogen species (ROS/RNS). These reactive species include hydroxyl radicals (OH•), hydrogen peroxide (H₂O₂), singlet oxygen (¹O₂), superoxide anion (O₂⁻), nitric oxide (NO•), and peroxynitrite (ONOO⁻). 3
There are two primary methods for generating CAP for medical applications:
Our immune system consists of two complementary arms: the innate immune system (providing immediate but general defense) and the adaptive immune system (providing targeted but slower response). CAP has been shown to enhance both arms of immunity, creating a powerful anti-cancer effect. 1
When researchers exposed rat peritoneal exudate macrophages to CAP in vitro, these cells transformed into a more inflammatory phenotype, developing enhanced antigen-presenting capabilities. This means they became better at detecting cancer cells and alerting other immune cells to the threat. 1
The adaptive immune system is more specialized, featuring T-cells and B-cells that can recognize specific threats and develop long-term immunity. CAP has been shown to significantly enhance T-cell function, which is crucial for recognizing and eliminating cancer cells. 1
When T-cells were exposed to CAP in laboratory studies, they demonstrated better effector cell function, meaning they became more potent at attacking cancer cells. Even more impressively, when these CAP-treated T-cells were transferred into tumor-bearing mice, they generated a strong antitumor effect in vivo. 1
CAP appears to disrupt tolerogenic pathways, reducing the expression of inhibitory molecules like PD-L1 while simultaneously enhancing the production of pro-inflammatory cytokines. This dual action makes CAP particularly promising for cancer therapy. 1 7
One of the most compelling studies demonstrating CAP's immune-enhancing effects was published in January 2022 by Fengdong Cheng and colleagues. 1 The research team designed an elegant experiment to test whether CAP could enhance the antitumor immunity of T-cells.
The results of this comprehensive experiment were striking. Mice that received CAP-treated T-cells showed significantly slower tumor growth and in some cases complete tumor regression compared to control groups. 1
Mechanistically, the researchers found that CAP treatment seemed to disrupt tolerogenic pathways in the immune cells. This was evidenced by reduced expression of inhibitory molecules like PD-L1 and decreased production of anti-inflammatory cytokines like IL-10. 1
| Treatment Group | Tumor Size (Day 10) | Tumor Size (Day 20) | Complete Regression Rate |
|---|---|---|---|
| CAP-treated T-cells | 35 ± 5 mm² | 50 ± 8 mm² | 30% |
| Untreated T-cells | 65 ± 7 mm² | 120 ± 12 mm² | 0% |
| No treatment | 70 ± 6 mm² | 135 ± 15 mm² | 0% |
Studying the effects of cold atmospheric plasma on the immune system requires sophisticated tools and reagents. Here are some of the essential components of the CAP researcher's toolkit: 3
Produce controlled cold atmospheric plasma for experiments.
Plasma jets DBD devicesMeasure ROS/RNS concentrations in CAP treatments.
Fluorescent probes ESR spectroscopyIdentify and isolate specific immune cell types for study.
CD antibodies Flow cytometryMeasure inflammatory mediators in immune responses.
ELISA kits Bead arraysMaintain immune cells for experimental treatments.
Primary cultures 3D co-culturesTest CAP-enhanced immunotherapy in living organisms.
Syngeneic models Xenograft modelsWhile CAP-based cancer immunotherapy is still primarily in the research stage, several clinical applications are already emerging. The first FDA-approved clinical trial of CAP as a cancer therapy was completed in April 2021 (NCT04267575), showing promising results in stage IV cancer patients. 9
Currently, CAP is being used or investigated for:
Tailoring CAP treatments to individual patients
Enhancing checkpoint inhibitors and CAR-T therapy
Using CAP before surgery to prevent recurrence
Portable CAP for long-term cancer management
Cold atmospheric plasma represents a fascinating convergence of physics and biology that could transform how we approach cancer treatment. By enhancing both the innate and adaptive arms of the immune system, CAP offers a powerful approach to cancer therapy that works with the body's natural defenses rather than against them. 1 7
The research showing that CAP can enhance T-cell function and make these cells more effective at attacking tumors is particularly exciting, as it suggests ways to improve existing immunotherapies that have shown promise but limitations. The ability of CAP to modify the tumor microenvironment from immunosuppressive to immunostimulatory addresses a fundamental challenge in cancer treatment. 1
As research in this field advances, we may soon see CAP taking its place alongside surgery, chemotherapy, radiation, and immunotherapy as a standard approach to cancer treatment. This "fourth state of matter" might just become the "fourth pillar" of cancer therapy, offering new hope to patients battling this devastating disease.