What is Immune System and Immunotherapy?

The principle of immunotherapy is based on treating cancer using our own immune system. The goal is to allow the body's defenses to attack cancer cells effectively.

What is the immune system?

The body can defend itself against external attacks (bacteria, viruses) by activating its immune system. The mechanisms involved during its mobilization are complex since it can call on various types of cells and produce different defense molecules.

The immune system can be compared to a real army with two lines of defense. The first called "innate immunity, "devoid of memory, which constantly watches to detect the slightest anomaly (abnormal cells, tumors, or infected by a virus). The second called "adaptive immunity that takes more time to set up. It is directed against a specific enemy. A property that imposes the learning phase lasting several days during which the immunity cells learn to recognize the target will be eliminated. This learning allows adaptive immune cells to keep the enemy's profile in memory to act immediately during a second attack from the same enemy. This second type of immunity develops over the years. There is a fact that explains why young children are more susceptible to infections. Finally, the principle of vaccination is based on the ability of the immune system to memorize.

For further

The learning process required to trigger an adaptive immune response is long. First of all, it is necessary to locate the enemy and isolate a characteristic fragment, that is, allowing him to be recognized every time, called "antigen." This mission is performed by the dendritic cells. The latter is, in fact, capable of cutting the target into pieces to isolate the antigen. Once found, the antigen is taken over by the major histocompatibility complex present on the surface of dendritic cells to present the antigen to the immune system.

When dendritic cells present an antigen on their surface, they travel to the lymph nodes (the headquarters of cells of the immune system). The presented antigen makes it possible to train the immune cells (T lymphocytes or B lymphocytes) to recognize the enemy to be eliminated. When a T lymphocyte is in contact with an antigen for the first time, a reaction of multiplication and activation of the latter is triggered. Once several T lymphocytes are formed, they move towards the target to be shot down. On the other hand, B lymphocytes can secrete antibodies directed specifically against the antigen and serve to neutralize it. Thus, in nearly 48 hours, the body's immune system can eliminate any intruder (bacteria, virus, etc.) without any outside help. However, sometimes it may encounter some difficulty and fail. This is the case with tumor cells.

Cancer and the immune system

Cancer is always initiated by the alteration of the genetic material of one of the body's cells. Indeed, this one gradually loses control of its proliferation, becomes immortal, and multiplies in an anarchic way in the organism. Why do immune cells not respond effectively to tumor cells?

The immune system's inability to recognize a cancer cell has long been explained by the fact that it is programmed not to attack the cells of the self to avoid any risk of self-destruction. We are talking about autoimmunity. However, tumor cells are self- cells with an abnormality. However, it was later discovered that cancer cells had specific antigens on their surface that sometimes appear to be detectable by the immune system. Many avenues have been explored on antigens, without success.

In addition, cancer cells also can be able to camouflage themselves to make the body's immune system believe that they pose no threat. Sometimes cancer cells are able to take the initiative to block the action of immune defenses. Tumor cells escape the immune system, and it is by understanding how they do that that therapy can educate the immune system so that it can find and eliminate cancer cells.

What is immunotherapy?

Immunotherapy relies on using the immune system to kill cancer cells from the body, as it usually does with bacteria or viruses. This therapy teaches the immune system to recognize and destroy tumor cells. The immunotherapy represents a major hope in the fight against cancer. Although improvements are still needed, the numerous studies concerning immunotherapy are obtaining very good results. Several treatments are already available. At present, this therapy is never used alone as a first-line but can help eradicate the tumor.

For several years, various avenues have been explored to stimulate the immune system:

Injection of the anti-tuberculosis vaccine which is known to boost immunity;

The collection of lymphocytes, their multiplication in the laboratory and their reinjection into the patient;

The injection of cytokines (chemical messengers) capable of stimulating the immune system. However, they can cause high fevers.

Studies have also been done on the modification of cancer cells. These were rendered harmless by irradiation in the laboratory and then re-injected into the patient. The difficulty was modifying the cell enough to boost immunity without modifying it too much so that it did not differ too much from other cancer cells. They remained recognizable by the immune system.

In practice, a distinction is made between local immunotherapy and general immunotherapy. Local immunotherapy is used for bladder cancer that tends to come back after surgery. It is based on the injection of the anti-tuberculosis vaccine into the bladder.

General immunotherapy consists of injecting substances (interferon and interleukin 2) normally secreted by lymphocytes in the event of aggression. These substances are produced by genetic engineering. In oncology, interferon is used to treat kidney cancer, leukemia, lymphoma, myeloma, or melanoma. Instead, interleukin two is used in two chemo-resistant cancers: metastatic kidney cancer or metastatic melanoma. Moreover, monoclonal antibodies (substances directed specifically against the antigens of tumor cells) are used in certain cancers such as chemotherapy-resistant malignant lymphoma or in certain forms of advanced breast cancer.

How does immunotherapy work?

Unlike chemotherapy or radiation therapy, it does not directly target the tumor but stimulates a patient's immune system to fight cancer on its own. Since cancer cells are initially normal cells, the immune system does not recognize them as abnormalities or too late to fight them.

According to doctors, "the cancer cell sends signals to the immune cells through checkpoints, to let them know that everything is fine and not to worry." As soon as we lift the camouflage, the immune system will be able to do its job. One of the immunotherapy strategies is to inhibit these checkpoints so that the normal binding of the defense system detects the abnormality and attacks the tumor cells.

What are the advances in this treatment?

In addition to this type of treatment, the first on the market against melanoma in 2011, more and more advances have been made. In 2015, the first drug for lung cancer also received the authorization. "Since then, there has been a real acceleration. The treatments fall one after the other". Advances go so far as to transform a patient's immune cells into cancer killers. This is the CAR-T cell method. The patient's T lymphocytes, whose role is to recognize and destroy abnormal cells, are removed and then genetically modified to add a chimeric antigen receptor (CAR) and allow them to recognize cancer cells more easily. "T cells are hit, killers. They recognize and then destroy it. Modified, they become much more effective". This method is particularly effective in leukemia, and it is still in clinical trials. Currently, immunotherapy has shown success against cancers of the lung, cervix, blood, skin, and even prostate. Today, doctors have cure 30% of patients with melanoma that we could not have treated before. Now, according to studies made public at the Chicago convention, patients with lung cancer are treated with immunotherapy rather than chemotherapy.

What are the limits?

This does not mean that the old treatments are to be abandoned, and it is still difficult today to do without chemotherapy. "Immunotherapy works very well, but in only one type of patient. We don't always know why it works or why it doesn't. " The side effects are not to be overlooked. While the most common effects are pimples and diarrhea's development, the immune system can attack any cell in the body, including vital cells. "If a patient is short of breath, for example, it is not necessary to wait and stop the treatment, "explains the researcher, who specifies that immunotherapy is generally better tolerated than chemotherapy. Above all, the latest studies show the value of combining the different types of treatment, including the different immunotherapies, as was the case for this first cure for a patient with breast cancer.

Are there any side effects? 

"Yes! But there are not shown in all patients. Only 10% have severe toxicities. These side effects are completely different from toxicities caused by chemotherapy.” Concretely, no hair loss, nausea/vomiting, and infections were observed. It is also not useful to insert a central line or to perform transfusions. At the moment, the only side effects to report are inflammation or autoimmunity. Logical reactions "since we stimulate the immune system, and which are treated by taking anti-inflammatory drugs. The experts also wish to specify that "the quality of life of patients has been shown to be better in clinical trials," due to immunotherapy.

Depending on the case, more effective results than chemotherapy

Active immunotherapies have already proven their worth in reducing the size of tumor lesions (primary tumors or metastases) and even making the disease completely disappear in relapsing patients, on which current treatments did not work. On average, 20% of patients see their disease regress. In addition to this result, there are patients whose disease has stabilized for a long time.

Author: Vicki Lezama