Immunotherapy is already responsible for waking up the immune system to attack tumor cells. It revolutionized the prognosis of some very aggressive tumors in the last decade and aims to achieve the same in other non-oncological pathologies.
Although research is still in its beginning stages, the first results are encouraging. The Institut de Recerca de Barcelona (IRB) gathered a group of experts to address this new paradigm and, during the meeting, studies on mice have been put on the table to show the potential efficacy of new drugs to combat Parkinson’s or pulmonary fibrosis, among other conditions.
But the use of this treatment does not limit its application to treating cancer. The concept that researchers handle is the same. In cancer, tumor cells play a clue and wear a kind of disguise in the form of proteins that stick to the surface of cells, such as PDL-1, and block the function of lymphocytes. This allows them to camouflage and circumvent the immune system.
What immunotherapy does is remove that disguise from bad cells and reactivate lymphocytes to attack.
Many diseases linked to aging consist of the accumulation of aberrant cells. They are not proliferative, but degenerative and abnormal cells. There is a suspicion that they also hide from the immune system.
At the event held in Barcelona, researchers focused on diseases related to aging, such as Alzheimer’s or pulmonary fibrosis, pathologies where the first investigations have already paid off.
The hypotheses used by the researchers point to two situations: either the damaged cells manage to escape from the immune system, as is the case with the tumor cells, or the lymphocytes, due to age, are more stunted and unable to detect threats precisely.
In any case, the age factor also influences the risk of cancer, but there is an important difference: aberrant cancer cells have mutations; those of degenerative disease, on the other hand, do not.
The immune system not only recognizes mutations but also proteins that we have silenced in the body. The ICREA researcher works in the study of the so-called senescent cells. That is, damaged cells that the body should have eliminated but, for some reason, are still there. Apparently, the immune system is not doing its job.
With age, in addition, the body’s repair capacity is lower. The immune system becomes less effective. The difference between cancer and other diseases is that in the latter, there are no malignant cells. What fails in them is the capacity to repair.
In pulmonary cancer, for example, scientists knew that COPD was a self-inflicted tobacco disease. Now, they know that COPD occurs in 50% of cases, but there are other causes, such as poor lung development, prematurity or malnutrition in childhood, which also influence the outcome.
Tobacco remains the most important risk factor but there are other causes and that opens up new treatment opportunities. There is already data that indicate that if a person smokes, the result is lung inflammation and, by inflaming them, they can produce substances that function as antigens and that cause a response against the immune system.
As of now, researchers still have more questions than answers when it comes to the right treatment. The first studies in this field date back two or three years ago, but the evidence that they are on the right track is already on the table.
The dangerous cells, initially, were cancer. Now we find dangerous cells in pulmonary fibrosis, hepatic or renal fibrosis, etc. These bad cells are like precancerous cells that begin to expand uncontrollably.
As they expand, certain warning signs appear on the surface. This is what causes the disease but at the same time it shows a target for the immune system to attack when patients begin treatment.
Some immunotherapeutic drugs, with the same mechanism of action used in cancer, have already shown their effects with experiments on mice.
In 2016, a group of researchers published a study on Nature which showed that by blocking the PD-1 – one of those brakes that are placed on the lymphocytes to neutralize them -, the immune system manages to eliminate beta-plaques, Alzheimer’s characteristics, and improve cognitive performance.
The meeting in Barcelona also presented results related to pulmonary fibrosis. It was explained how, in pulmonary fibrosis, these degenerative cells hide expressing the same factors that cancer cells express in hiding: PDL-1.
They have seen that if they treat cells with an antiPDL1 the mouse’s immune system reactivates and kills these degenerative cells and the disease is much less severe.
Many of the treatments we give for other diseases are already based on immunotherapy, only less selective than these therapies, which are of high complexity,” adds Manel Juan, head of the Immunology Section of the Hospital Clínic.
The immunologist considers that, although in cancer it is a mutation that causes lymphocytes to not recognize the tumor cell, in other diseases it is the immune system itself that is not functioning properly.
Juan also has studies underway to test the CAR-T therapies – modified cells in the laboratory from each patient’s T-lymphocytes, adding a gene that helps them identify the malignant cells to destroy them – in another disease other than cancer, like pemphigus; a dermatological condition that causes sores and blisters on the skin.
Researchers admit that it is still too early to transfer these findings to clinical practice, because knowing that the immune system participates, at least, in 80% of diseases, there must be the solution out there for all those situations.