"Around 2050, almost all tumors will be treated with immunotherapy of some kind. We will have conquered cancer ". These are the words of the Nobel Prize winner for medicine 2018 Tasuku Honjo, of the University of Kyoto, who at the Karolinska Institutet Swedish, continues to report to journalists: "I can not say when with certainty. But in less than twenty years, many patients have been treated completely with immunotherapy. And now there are many more involved ". The American colleague James P Allison of the University of Texas echoes him, with whom he shares the prize: "Soon we will get rid of some types of cancer, melanoma, for example. They will not disappear completely, but there will be effective treatments, increasing life expectancy. Some are already about to disappear ".
Allison and Honjo were the two pioneers who laid the foundations of a strategy to fight cancer: unleashing our own immune system against cancer cells. Already in the past this line had been investigated experimentally, trying to strengthen and stimulate our defense system and directing it to cancer cells that are multiplying in an uncontrolled way, but without convincing results. We had to wait for the discovery of particular molecular mechanisms that regulate the functioning of the immune system, thanks to Honjo and Allison in the Nineties. "The idea that we could fight cancer by simply ignoring the tumor and focusing instead on the immune system amazed me," says Allison during the lectio magistralis for the awarding of the Nobel Prize.
The one on which the two scientists focused their attention, in fact, does not concern the stimulation of the immune system, but rather the removal of the brakes that make it incapable of fighting the tumor. In fact, Allison and Honjo have discovered two immunological checkpoints, two receptors on the surface of T lymphocytes, which are able to act suppressively in the complex mechanism of balance that regulates the immune system and gives the answer. They are Ctla-4, identified by Allison, and Pd-1, discovered by Honjo, and act as brakes that make life simpler to the tumor, slowing the attack of T lymphocytes. The two researchers worked independently and managed to develop monoclonal antibodies able to block this inhibitory action and then trigger the immune system against tumors (not without side effects to be controlled). Their work, especially on melanoma that has become a model for other researchers, paved the way for what became the fourth pillar of anticancer therapy (along with surgery, chemotherapy and radiotherapy) against several other types of cancer - such as those lung and breast, bladder, kidney and prostate carcinomas, lymphomas and leukemia - which earned Honjo and Allison the Nobel.
The future of immunotherapy, however, recounts the Nobel prizes to journalists, is in combined therapies, different pharmacological strategies accompanied by aggressive treatments such as chemotherapy and radiotherapy. "There are over a thousand combined therapies currently underway. The publications already exist: if you destroy the immune system, tools like chemo and radiotherapy work less. The power of the immune system is the basis for fighting cancer, "says Honjo. "Combinations of three or four drugs are coming together," continues Allison. "Usually with cancer you try to kill all the cancer cells, thanks to chemo and radio you can kill most of them, while the immune system can do the rest."
However, it remains to be discovered why immunotherapy does not work for some patients. "In 40-50% of cases with melanoma or lung cancer the patient does not respond to therapy: sometimes resistance is from the beginning, while others grow over time", says Michele Maio, director of the Center for Immunology of the Santa Maria Polyclinic. at the Scotte di Siena on the sidelines of a meeting organized in Stockholm by the Roche Foundation. "The purpose of research over the next four or five years is to find out why and identify patients in whom immunotherapy will respond better". But not only. In addition to studying the immune system, the tumor and the environment that surrounds it, in fact, another effort should focus on the microbiota, the set of microorganisms living with us. "The intestinal flora can regulate the functioning of the immune system," continues Maio: "A certain composition of the microbiota promotes immunotherapy, so we could act on the flora to make it more effective".
While immunotherapeutic research continues, today the 2018 Nobel Prizes are celebrated: the two scientists Tasuku Honjo and James Allison who, with almost 900 thousand euros of the prize to be divided, intend to