Cancer immunotherapy: definition, indications, effectiveness

Immunotherapy, what is it?

Surgery, radiotherapy, chemotherapy… The arsenal of anti-cancer treatments has long been based on these three ways of eliminating tumor cells. But cancer research has been using a new approach called immunotherapy for several years. It involves mobilizing the immune system to use the patient’s natural defenses and destroy the cancer cells themselves.

“This is a major paradigm shift in cancer treatment. Professor Eric Solari defines, oncologist and member of the Scientific Council of the ARC Foundation, because until now we used the main targeted therapies (surgery, radiotherapy, chemotherapy) to directly attack the diseased cells with the aim of destroying them. For the first time, with immunotherapy, instead, we have a treatment that will seek out ‘non-diseased’ cells, bring them in and teach them to eliminate tumor cells.”

In immunotherapy, it is therefore the body’s own healthy cells that will be enhanced or modified by various principles to recognize and destroy cancer cells.

What are the different forms of immunotherapy?

Over time and research, this concept of immunotherapy is expanding and different strategies are being identified and tested. Therefore, we can talk about immunotherapies in the plural.

Marrow transplantation

“The first immunotherapy in practice dates back to the 1950s when the first donor bone marrow transplant was used in leukemia.” reveals the oncologist. Therefore, bone marrow allograft is a form of immunotherapy that alters the patient’s immune system.

Immunomodulators

In some cases, cancer cells are able to evade immune defenses. Then immunomodulation strategies were implemented. It is the main immunotherapy used to date. Professor Solari explains the mechanism as follows: “When tumor cells develop, they express proteins on their surface that block the immune system and prevent it from functioning. Depending on the tumor, an injected or given antibody then binds to these blocking molecules and lifts the inhibition. These are called checkpoint inhibitors. “Once the blockage is cleared, the immune system goes back to doing its job against the tumor cells.”

Several immunomodulators are being tested in France against various cancers, usually given intravenously:

• Nivolumab (anti-PD-1): melanoma; non-small cell lung cancer; clear cell kidney cancer; Hodgkin’s lymphoma; squamous cell carcinoma of the head and neck; urothelial cancer (bladder and urinary tract);
• Pembrolizumab (anti-PD-1): melanoma; non-small cell lung cancer; Hodgkin’s lymphoma; urothelial cancer; squamous cell carcinoma of the head and neck; clear cell kidney cancer;
• Atezolizumab (anti-PD-L1): urothelial cancer; non-small cell lung cancer;
• Durvalumab (anti-PD-L1): non-small cell lung cancer;
• Avelumab (anti-PD-L1): Merkel cell carcinoma; kidney cancer.

Car-T cells

Since 2019, a third type of immunotherapy has been emerging, called cell therapy or CAR-T cells. The highly personalized CAR-T system involves taking a patient’s immune cells, genetically modifying them in the lab to weaponize them against the tumor, and injecting them back into the patient. “In practice, sometimes in a laboratory at the end of the world, it is quite a difficult process for the patient to recover their cells, work on them and inject the patient again. But it’s a process with important results.” confirms the oncologist.

Many trials are also ongoing that are regularly shared on Doctissimo, such as virotherapy, which involves injecting a virus directly into a tumor that destroys tumor cells. “But the level of evidence is not clear yet.” the professor announces, but the scientific community is constantly learning about it.

Immunotherapy: against which cancers?

Immunotherapies today offer innovative and particularly effective approaches in the fight against cancer, recognizes the Arc site. “Immunotherapies have begun to work in several different cancers. Specifically in metastatic melanomaA serious form of melanoma, which was a fatal disease a few years ago, today we save a lot.” Good results from the side should also be noted Lung cancerand in many tumors in general.

“We can give many examples, immunotherapies work in many cases… But not in all, not always” Professor Solari recalls. For example, therapy has failed in pancreatic cancer. “It also doesn’t work for everyone, and we’re trying to figure out why.”

Who can benefit from immunotherapies?

Effectiveness only applies to a minority of patients known as “responders”. For checkpoint inhibitors, the ARC Foundation lists an average of only 30% responders; 20% for hepatocarcinoma… except for Hodgkin lymphoma and its 70% response.

The offer of immunotherapy treatment does not apply to all cancer patients and therefore depends on the circumstances. “Today, there are tumor types that we know respond well, so we start offering first-line immunotherapy to patients as soon as we know they have a high enough response rate.” the oncologist explains.

But the choice also depends on the patient: “Interfering with a person’s immune system also means taking the risk of side effects. Therefore, there is a research program for biomarkers, predictive signatures of response to immunotherapy, to avoid giving a person who does not respond positively to immunotherapy. This is an ongoing program, we are moving forward slowly.”

As the National Cancer Institute reminds us, immunotherapy may be offered when other treatments have not worked. In the treatment of some melanomas, specific immunotherapy with monoclonal antibodies is indicated:

• Phase III in clinical trials;
• non-operative stage III;
• stage IV.

Can immunotherapy be combined with other treatments?

Immunotherapy also has the advantage that it can be combined with other treatments, such as chemotherapy or radiotherapy, sequentially rather than simultaneously to better target the tumor. Combinations are also being tested, for example, with targeted therapies that may have an effect on angiogenesis (the formation of blood vessels that supply a tumor). “In some cases, we can use 2 immunotherapies with 2 blocking antibodies at the same time, but not the same target, and it works well. We often gain efficiency” expert confirms.

What is the current study?

Research in immunotherapy focuses specifically on the response of some patients and not others. Thus, new ways are learned.

• The expression of immune cell inhibitors is a topic that has been extensively studied but is currently lacking in clarity;
• Mutational load (i.e., quantification of tumor DNA mutations) is another biomarker of interest, but remains imperfect to date;
• Characterization of circulating immune cells is in progress. Some populations may indeed predict patient response;
• Microbiota research is another area of ​​research where the presence of different types of bacteria can have a direct impact on the effectiveness of immunotherapy.

“We don’t know all the possibilities of immunotherapy yet, but obviously we’re always learning.” Professor Solari concludes.