Understanding Cancer

Our bodies are made up of cells. Groups of cells form tissues—for example, muscles or skin—and groups of tissues make up organs such as the heart, lungs, or liver. Each organ has a specific job, and together they make sure the body stays alive and works properly. But for everything to keep running smoothly, our cells must stay healthy. Since cells age and stop working well, they need to renew themselves. Old cells die, and new ones take their place. Every day, in the body of an average adult, roughly 330 billion cells die and are replaced by new ones. Over the course of a year, nearly 30 kg of new cells, about as heavy as a small Labrador, are renewed [1]!

But what happens if the old cells do not die, and new ones keep forming? Well, then, people get clumps of cells that grow uncontrollably. If these clumps stay in one place and do not spread, they are called tumors. If the cells are dangerous, meaning they can invade other parts of the body and make a person sick, that is called a malignant tumor or cancer. These cell masses damage the surrounding tissues, spreading across the body and causing the organs to stop working as they should.

How Sneaky Cells Trick the Immune System

Cancer usually happens because of damage to the DNA (the “instruction manual” inside each cell), which tells a cell to keep dividing when it should not. Usually, the body’s immune system identifies those malfunctioning cells and destroys them (Figure 1). The immune system is the body’s natural defense network: a complex system of cells, tissues, and organs that constantly monitors the body to identify and eliminate anything harmful, including viruses, bacteria, and cancer cells. In theory, the immune system should spot and destroy cancer cells before they can cause trouble. But cancer cells are sneaky. They grow super-fast and have learned clever ways to hide from the immune system, kind of like wearing an invisibility cloak! To do this, they use the three Cs rule: camouflage, cytoprotection, and coercion [2]. Just like a chameleon changes color to match the leaves around it, cancer cells use camouflage to hide inside the body so the immune system cannot find them. “Cyto” means cell—using cytoprotection, cancer cells create a kind of shield to protect themselves from immune cells trying to destroy them. Coercion describes how cancer cells can even fight back, using special “weapons” to weaken the immune system’s attack. Because of the three Cs, malignant tumors can grow quietly without being stopped by the immune system (Figure 1).

The Secret Message Cancer Cells Send When They Die

What if we told you there is a way to wake up the immune system and give it a “map” to help it find the hidden cancer cells and destroy them? The coolest part is that the map is given to the immune cells by the tumor cells themselves! This amazing process is called immunogenic cell death (ICD). When cancer cells die through ICD, they send out special signals that act like flashy lights, showing immune cells exactly where they are hiding. They also show their unique “flags”: special proteins that only those cancer cells have. These flags are like ID badges. Dendritic cells, the detectives of the immune system, find the dying cancer cells, pick up these flags, and show them to the T cells, which are the elite fighter cells. With this information, the T cells know exactly which cells to attack, leaving healthy cells unharmed (Figure 2) [3].

Once the immune system has learned the cancer’s flags it remembers them, creating a lifetime memory. If the cancer ever tries to come back, the immune cells recognize it instantly and strike fast. In this way, ICD turns dying malignant tumor cells into teachers, training the immune system to spot, target, and remember the villains so the body can fight them more effectively.

Killing Cancer With Light?

Now you might be wondering: if cancer cells protect themselves with the three Cs, how can doctors trigger the ICD process? Simple: they use specific drugs that kill cancer cells and at the same time “unmask” them, as we just described (Figure 2). Indeed, over 20 years ago, scientists discovered that some chemotherapy drugs could actually activate the immune system, not just kill cancer cells. Later, they found out this effect came from ICD!

One of the first drugs found to do this is doxorubicin, which is still used today to treat cancers including leukemia and breast cancer. Since then, scientists have found more ICD inducers—like oxaliplatin, mitoxantrone, bortezomib, and even radiation therapy. To trigger ICD, a drug must first create oxidative stress, like sudden bursts of energy chaos inside the cell. This energy chaos sets off special pathways that turn on the cell’s “flare lights”, which signal the immune system to come to the rescue.

Another way to trigger ICD is through photodynamic therapy (PDT). PDT uses drugs called photosensitizers that are harmless until they are hit by light of a specific wavelength. The drugs absorb the light’s energy and cause oxidative stress, like an energy wave, that kills cancer cells, possibly through ICD. The basic principle of using light and chemicals to heal dates back thousands of years to ancient Egypt and India, where sunlight and plant extracts were used to treat skin diseases. Basically, ancient healers made people eat seeds or leaves of certain plants that are full of photosensitizers, and then exposed their skin to sunlight [4]. Then, over 120 years ago, two German doctors used PDT for the first time to treat skin cancer patients. Many years later, scientists noticed that the immune system of PDT-treated patients are more active, leading to the realization that PDT can also help “wake up” the immune system to fight cancer by ICD.

Patients can receive photosensitizers as a cream (for skin cancers), as a tablet, or as an injection. After receiving the drug, the patient waits several hours or sometimes a few days. This time is needed to allow the photosensitizer to build up in tumor cells. When the right time has passed, doctors shine light with a specific energy on the tumor. The light activates the drug, which then causes oxidative stress in the tissue and destroys the tumor cells. The effectiveness of PDT depends on the type of cancer and where it is located. There is no single success rate for all cancers. For some types of basal cell carcinoma (a common type of skin cancer), studies show that 70%-77% of patients stay free of cancer 5 years after PDT.

Advantages of PDT

Because the light can be precisely directed and the drug only becomes active where the light shines, PDT targets malignant tumors selectively, while sparing surrounding healthy tissue. The procedure does not hurt the body as much as surgery does, so it helps people heal faster. If a tumor is in a delicate place—like near a person’s eyes or on their face—doctors use PDT because it leaves almost no scars and does not damage the function of the body part. Another advantage is that PDT still works great even if a tumor comes back after other therapies, like chemotherapy, have already been tried. If the tumor comes back after PDT, doctors can safely give it several more times.

However, PDT also has its limitations. If the photosensitizer is not taken up only by the cancer cells but also by healthy cells, patients must avoid sunlight for several days, since leftover drug in the skin could cause burns or rashes. Moreover, the light used to activate most photosensitizers can only penetrate a few millimeters into tissue, making PDT most effective only for surface or shallow cancers (Figure 3).

To overcome this challenge, scientists are now developing next- generation photosensitizers that can be activated by light of higher (near-infrared) wavelengths. These longer wavelengths penetrate deeper into tissues, potentially allowing PDT to reach and treat cancers located beneath the surface. This could expand the use of PDT to more complex or internal cancers. Even with its current limitations, PDT remains an elegant weapon in the fight against cancer—one that unites ancient healing wisdom with cutting-edge science, using the timeless power of light to destroy disease.

Restoring Balance Through Light-Driven Immune Control

In the end, balance is of ultimate importance. Our bodies are made of countless cells that live, die, and renew in a continuous rhythm to keep us alive. Cancer disrupts that harmony. In cancer, the body’s own cells “rebel”, learning to hide, protect themselves, and manipulate the immune system for their own benefit. Yet science has found a way to restore the body’s balance by helping the body remember its own power. Through ICD, dying cancer cells can become messengers instead of mere targets, teaching the immune system how to recognize and fight the invaders from within. What began thousands of years ago with sunlight and plants has evolved into a therapy that blends ancient wisdom with scientific innovation. This is a reminder that, sometimes, the best way to fight darkness is simply to turn on the light and believe in inner strength.

Glossary

Immune System: ↑ A network of cells and organs that protects the body by detecting germs, viruses, and abnormal cells, then activating defender cells like T cells to attack harmful invaders.

Camouflage: ↑ A strategy used by cancer cells to hide from the immune system, making them look like normal cells so they are not attacked.

Cytoprotection: ↑ A strategy by which cancer cells protect themselves from damage or death, even when the body or treatments try to destroy them.

Coercion: ↑ A mechanism through which cancer cells actively influence immune cells, reducing their ability to attack the tumor or even redirecting them to support tumor growth.

Immunogenic Cell Death (ICD): ↑ A special kind of cell death in which dying cancer cells release alarm signals that help the immune system notice the tumor and mount an attack.

Oxidative Stress: ↑ A condition in which harmful molecules called reactive oxygen species (ROS) build up in cells and damage important components like DNA, proteins, and lipids.

Photodynamic Therapy: ↑ A cancer treatment for cancer that uses light to activate drugs called photosensitizers inside the body, causing harmful molecules to form and damage or kill nearby cancer cells.

Photosensitizer: ↑ A drug that becomes activated when exposed to light (specific for each photosensitizer), leading to oxidative stress, which in turn kills cells.

Conflict of Interest

The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Acknowledgments

This research was funded by the H2020 Marie Skłodowska-Curie Postdoctoral Fellowship (call HORIZON-MSCA-2022-PF-01) under the project 101108930 entitled “Generation of tumor neoantigens with photodynamic therapy: a new strategy for anticancer vaccines to fight head and neck cancer.”

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