What is Immunotherapy? How is Immunotherapy Applied?

There are ongoing developments in cancer treatment every day. In addition to chemotherapy and radiotherapy methods that have been used for many years, immunotherapy, a type of treatment using drugs, has begun to provide longer-lasting control over cancer in recent years. By activating a person's immune system, immunotherapy enables the individual's own immune cells to fight cancer cells more effectively.

Immunotherapy, which activates the immune system consisting of white blood cells (WBCs) and the tissues and organs of the lymphatic system, can also be defined as a type of biological therapy. Various immunotherapy methods have been attempted since the second half of the 1800s. However, recent technological advancements have led to better recognition of cancer cells, resulting in immunotherapy methods that use drugs to regulate the molecules on cancer cells and immune cells, known as “checkpoint” inhibitors, providing long-term control and even complete remission for many diseases. Nowadays, when we talk about immunotherapy, we refer to checkpoint inhibitors; we will discuss these in detail.

What is Immunotherapy?

Cancer cells, which are made up of the body's own cells, have different structures than healthy cells. Therefore, the body’s defense system fights against cancer cells. However, cancer cells can evade detection by the immune system by undergoing certain changes. The ability of cancer cells to hide stems from the proteins they carry. Additionally, cancer cells can undergo mutations, making it easier for them to evade the immune system's defense. As a result, the ability of the body’s own immune system to destroy cancer cells diminishes or is completely lost. Immunotherapy is a form of biological therapy. In other words, the drugs administered during immunotherapy activate the individual’s own immune system. The activated immune system recognizes and destroys cancer cells.

What are the Types of Immunotherapy?

Immunotherapy, which facilitates the activation of immune system components such as macrophages, NK cells, and T lymphocytes, is essentially a treatment aimed at strengthening the person's immune system. Some commonly used immunotherapy methods include:

• Checkpoint Inhibitors: These drugs provide dramatic improvements in many cancers and are increasingly being used. These special molecules eliminate the natural brake mechanism in the immune system, allowing for the activation of T cells that recognize and attack cancer cells. In other words, these molecules work by blocking the ‘checkpoint proteins’ that stop the immune system from attacking cancer cells.

Other previously used immunotherapy methods include:

• T Cell Transfer: In T cell transfer, T cells found in the patient's cancerous tissue are taken and multiplied in a laboratory. The T cells transferred to the patient allow the immune system to respond to cancer cells again.
• Cytokines: Cytokines produced by immune system cells play an important role in the activity of immune system cells. They bind to cell receptors and promote cell proliferation. In immunotherapy methods applied subcutaneously, intramuscularly, or intravenously, cytokines such as interleukins, interferons, and GM-CSF are commonly used. This stimulates the proliferation of immune system cells while disrupting the formation of blood vessels that nourish tumors.
• Monoclonal Antibodies: This type of protein facilitates the immune system’s recognition of cancer cells by marking them. Monoclonal antibodies also prevent the proliferation of cancer cells and can sometimes be administered with radioactive substances to the body. This allows for targeted radiotherapy. In some cases, different cancer drugs are loaded onto monoclonal antibodies, ensuring that the cancer medication reaches the cancer cells directly.
• Viruses: Certain viruses known as oncolytic viruses can destroy cancer cells without harming healthy cells when administered to the body. They can also direct the immune system.
• Adjuvants: Adjuvants can be explained as substances that trigger antibody production. They are immune system agents that stimulate the production of antibodies.
• Interferons: Interferons (IFN), produced by the body itself, disrupt the proliferation mechanisms of cancer cells to slow tumor growth.
• Interleukins: Interleukins (IL), produced by the body, promote the rapid division and maturation of immune cells. They also increase the amount of antibodies produced against cancer cells.

When is Immunotherapy Applied?

In recent years, especially checkpoint inhibitors are being used alongside chemotherapy and radiotherapy or on their own. Initially, they were only used in metastatic (advanced) stages, but now their use in early-stage cancers alongside chemotherapy is also common. This allows for longer-lasting improvement and control of the disease.

How is Immunotherapy Applied?

Immunotherapy, known as checkpoint inhibitors, is administered intravenously, similar to chemotherapy. There is no special preparation required before the application.

What are the Side Effects of Immunotherapy?

Unlike classical chemotherapy drugs, immunotherapy medications do not cause hair loss. However, because these drugs enhance the immune response, they may mistakenly recognize healthy cells as foreign, leading to problems with the kidneys, intestines, endocrine glands, liver, and other organs. The most common side effects include diarrhea and hypothyroidism.

Who is Treated with Immunotherapy in Cancer, and for How Long?

The applications of immunotherapy vary depending on the type and stage of the disease. To determine which patients are suitable for immunotherapy, specific molecular tests must be conducted on pathology blocks from the patients in certain cancers (such as PDL-1, MSI, or TMB). In some tumors, immunotherapy may be used without the need for special testing. The patient's doctor determines whether the individual is suitable for immunotherapy based on these results and the findings of relevant studies.

In many studies, theoretically, patients can continue immunotherapy indefinitely as long as the disease remains stable and there are no side effects. Some studies are evaluating the effects of shorter-term use.

These treatments should be planned by a medical oncology specialist and administered to the appropriate patient at the right time.