Cancer resistance to promising immunotherapy

As a strategy to fight cancer, immunotherapy was – and is – the perfect plan for oncologists: to stimulate the body’s own defenses to identify tumor cells and attack them. Less aggressive than chemotherapy, more aimed at the tumor focus and with a potential for memory effect, these treatments have improved survival in tumors with a very poor prognosis and have become one of the great revolutions of the decade in the fight against cancer . So much so that its evolution has overwhelmed the scientific community, which is barely able to follow the rapid pace of this phenomenon in clinical practice. Doctors already have patients who live and are medicated longer than studied in the trials, some patients develop unexpected side effects and oncologists still cannot answer why immunotherapy works in some people and not in others. Experts agree that these treatments “have come to stay”, but there is still a long way to go: only 25% of tumors arrive.

The perfect cancer plan had been cooking for years, but something was wrong. As if it were a car, for many horsepower that researchers added to the immune system to make it stronger, the response was always insufficient. In the nineties, James P. Allison and Tasuku Honjo – Nobel Prize winners and parents of immunotherapy – gave a twist to that perfect plan and began to prove that, in order to reactivate the immune system, rather than reinforce it, it was necessary to lift the Brake. Honjo discovered molecules (PD-1) attached to the tumor cells, which served as a retaining wall on the immune system. Allison, on the other hand, also found other obstacles, the CTLA-4 proteins, and developed an antibody that could bind to them and block their immune system brake function. It took almost two decades to refine that concept and illuminate in 2011 the first immunotherapy, ipilimumab, against metastatic melanoma. Survival went from six months to years. Since then, the evolution of these treatments has been vertigo (there are currently about 2,000 trials underway with this therapeutic strategy).