What is cancer immunotherapy?
The treatment applied to activate the immune system or to reduce its effect to support the body’s fight against diseases such as cancer is called immunotherapy. There are also types of immunotherapy that target only certain cells of the immune system. Other types leave a general effect for the body. Some types of immunotherapy are listed below.
- Basil Calmette-Guerin (BCG)
- Some monoclonal antibodies
Immunotherapies are not only used in the treatment of cancer disease. However, its usage and importance for cancer has increased considerably in recent years. The immune system makes a great effort to separate normal cells and harmful cells. There are control mechanisms at the cellular level for this process to take place. In order to activate the defense system, the molecules that affect the control points must be active or passive depending on the situation. After 2011, drugs that activate the defense, which is a great breakthrough in the treatment of cancer, have been called immune checkpoint regulators.
‘Hidden’ immunity in Cancer Cells and Implications for Immunotherapy
The side effects of immunotherapy, which takes action against cancer, occur when the immune system also damages the normal cells of our body. Side effects occur more and more frequently in combined immunotherapy than in single-agent immunotherapies called monotherapy. As seen in most treatments, side effects in immunotherapy can affect almost every organ system. It mostly affects the intestines, hormonal system, skin, lungs. More rarely, it affects the cardiovascular system, the kidneys, the nervous system and the eyes. During the treatment, mild side effects usually occur, but unlike chemotherapy, the side effects may take longer and may last for months. Side effects of immunotherapy include diarrhea, mouth sores, skin allergies, fatigue, fever, weakness, vomiting, and nausea.
The first thing that comes to mind when this term is mentioned is the immune checkpoint regulators. These drugs activate the cells of the immune system by inhibiting the function of molecules on the cell surface called PD-1, PD-L1 and CTLA4. You can find the topics related to cancer immunotherapy on the following pages. The purpose here is to trigger the immune system to fight cancerous cells and put it in a strong position. Although the immune system is very important for our body, misdirections can lead to big problems. When it shows an uncontrolled and excessive performance, it can cause damage to various parts of our body. In an insufficient study, various diseases such as cancer may occur, with infections in the first place.
Types of Cancer Immunotherapy
Non-disease-specific immune activators
It was inspired by the Coley toxin and sought immune response against all forms of cancer. As a result, a non-specific response was obtained for the diseased individuals. These immunotherapies are still used today.
Bacillus Calmette-Guerin (BCG), the weak form of the bacterium that causes tuberculosis, is the first modern immunotherapy drug. BCG has started to be tested in cancer and it has been shown to be of great benefit, especially in the treatment of bladder cancer.
Cytokines, which are molecules that enable immune system cells to communicate with each other, appear as non-specific immunotherapy drugs. IL-2, one of the cytokines, is used in cancers such as kidney cancer and malignant melanoma.
Adjuvants in the group of non-specific immune triggers are generally used with vaccines to produce a more effective defense response.
Since the first group did not target a specific antigen, they constituted a general warning. Immunotherapies in this category target a specific antigen and are called specific immunotherapies. They are divided into two groups. Monoclonal antibodies bind to cancerous cells, allowing them to be recognized and destroyed by the defense system. Bispecific antibodies are proteins formed by two different monoclonal antibodies attached to each other.
Cancer vaccines are examined under two categories. These are preventive vaccines, which are prophylactic, and therapeutic vaccines, which are therapeutic. Therapeutic cancer vaccines developed for treatment form a strong defense against the cancerous cell. It aims to destroy the cancerous cell with genetically manipulated viruses. Protective vaccines, on the other hand, develop immunity against cancer-causing viruses called oncoviruses.
Immune checkpoint blocking
New mechanisms have been discovered that can activate the weakened immune system in individuals with cancer. Among these is the brake mechanism named CTLA-4. It was determined that the immune system of the patient with malignant melanoma shrank the tumor with the inhibition of CTLA-4.
After the discovery of molecules named PD-1 and PD-L1, which have a great effect on the immune system, drugs were produced against them. PD-1, a receptor found on the surface of immune cells, is called a cell death protein. PD-L1 is released from the cancer cell and binds to ligands and initiates the braking mechanism of the defense system. Nivolumab and pembrolizumab bind to these structures and inhibit the braking mechanism. The released defense system cells also take action to recognize cancerous cells and kill them.
This category includes modified lymphocytes and CAR T cells that infiltrate the tumor. In cellular therapies, as in others, it is aimed to activate the immune system.
Photoimmunotherapy is a treatment that aims to kill cancerous cells quickly and with minimal/no harm to normal cells with infrared light. In this treatment, scientists have created molecules that attach to monoclonal antibodies that recognize cancerous receptors and absorb light at a certain wavelength. The feature of the molecules here is that when they attach to the target receptor on the surface of the cancerous cell, the light in the tip is absorbed, enabling the molecule to become active.
Hyperthermia methods, especially the whole-body hyperthermia method, are applied to get the body’s fever, which is a response to natural immunity. In this method, lamps emitting infrared A rays with a depth effect water filter, which do not cause any harm to the skin, are directed directly to the body and abdomen. One of the purposes of this study is to activate the immune system like the others. In general, the range of 39-40 degrees is taken into account. Treatment varies according to the body’s response and reaching the intended heat. In recent studies, it has been reported that hyperthermia increases the expression of PD-L1 and PD-1, which are checkpoints on the surface of cancer cells. This means that the effectiveness of the immunotherapies to be applied will increase.
Radiotherapy, which is a regional treatment, leaves DNA damage in the cells in the targeted area and is expected to show its effect in the target area. In the concept defined as abscopal effect, radiotherapy can also be effective in places other than the target area. Although its mechanism is not fully understood, it is believed that it may occur through immunological mechanisms. When the dose is given effectively, radiotherapy can act like a tumor vaccine or it can cause immunological cell damage as well as death. The first cancer types that have this effect; lymphoma, leukemia, breast, neuroblastoma, melanoma and renal cell carcinoma. The appropriate dose and techniques of radiotherapy are still the subject of research.
The main feature of cancer cells is to spread and multiply very quickly. At this point, there are some advantages of immunotherapy targeting the immune system rather than the tumor. The tumor mutates very quickly and develops resistance to treatments such as chemotherapy are just a few examples. Combination therapies in immunotherapy promise more stable, long-term and potentially full recovery results. At this point, when used alone, it is still not at the expected level in many diseases. This is where the combination immunotherapies we mentioned above come into play and give hope to individuals.
If we come to the conclusion, cancer immunotherapy can be defined as a treatment method that is developing day by day. Apart from this, it should be kept in mind that resistance to immunotherapies can develop and this treatment method may not provide a certain benefit in all cancer types. It should not be forgotten that personalized therapy is a very important factor today, and it should be taken into account that the benefit of immunotherapy will differ from person to person.
Microbiota and Cancer Immunotherapy
Commensal bacteria (where one is in a positive state and the other in neutral) colonizing the gastrointestinal mucosal layer, that is, aggregating and proliferating, greatly influence the physiological functions of the host, including metabolism, cellular proliferation (rapid proliferation), immunity, and inflammation.
These effects allow bacteria to form small metabolites and molecules. It also coordinates the communication between the immune cell and the host at the intestinal barrier.
Many of the immunotherapies and current cancer treatments work by stimulating anti-tumor immune responses. However, whether the gut microbiota can influence the patient’s responses through the defense system is still a subject of research.
It is thought that the microbiota is of great importance in the occurrence and treatment of many diseases, including cancer, with ongoing studies. Studies have shown that the gut microbiota is a powerful treatment tool. With a better understanding of the role of the microbiota in carcinogenesis (the proliferation of a normal cell by turning into a tumor cell), its importance in the diagnosis, screening and treatment of cancer will increase to a great extent.
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