The lethal kiss between cancer cells and the human body's defenses

A group of researchers has illuminated a puzzling phenomenon.

When a human cell goes haywire and begins to multiply like crazy, threatening to start cancer, these evil daughters face the body's ever vigilant defenses.

Some white blood cells, such as NK (

) cells , are able to recognize and kill cancer cells.

The scientists, from the Ottawa Hospital (Canada), explain that, however, in some blood tumors, the fierce NK cells are numb after giving "a kind of kiss" to the cancer cells.

That

makes the defensive killer cells unable to kill the cancer cells.

Researchers have now discovered the mechanisms of this lethal caress that clears the way for cancer.

Kissing between

blood cells and other cells is common, as Italian immunologist Michele Ardolino explains.

The phenomenon is called trogocytosis, from the Greek

, meaning to nibble or gnaw.

The defensive cell comes into contact for a few minutes with another —which may be from a cancer or infected by a virus, for example— and steals a fragment of its membrane.

"My hypothesis is that immune cells have developed these mechanisms to be able to better sense their environment and be influenced by it," says Ardolino, who leads the Ottawa team.

Making proteins takes time and energy, so white blood cells steal them from neighboring cells to regulate their own behavior based on the outside, for example, when infected with a virus.

“It's like you're entering a baking contest and you're late for the competition.

You have the option of making your own dough for the cake or simply taking a pre-made one from the fridge”, illustrates Ardolino.

Sleepy

is a unique case of trogocytosis.

NK cells are amazing killers of cancer, but a protein called PD-1 prevents them from working properly.

Ardolino's team did not understand where that protein came from.

“Now we understand.

NK cells do not make their own PD-1 protein, but instead steal it from cancer cells!” he proclaims.

In the

, the NK killers steal a piece of tumor membrane that is laced with these soporific proteins.

According to the Italian immunologist, it is clear that some cancers take advantage of trogocytosis to override the defenses of the human body.

The discovery, after many experiments in mice with leukemia, was published this Wednesday in the specialized journal

.

Italian immunologist Michele Ardolino.Ottawa Hospital

Other cancer-killing white blood cells, T cells, do produce their own PD-1 protein, a natural brake that helps prevent them from attacking other normal cells in the body.

Ardolino recalls that there are already drugs directed against this PD-1 protein.

Some of them are among those that generate the most money in the world, such as Keytruda, a drug from the American pharmaceutical company MSD indicated against melanoma, certain lung cancers and other tumors.

Keytruda sales were close to 16,000 million euros in 2021, according to an analysis by the British company Evaluate Vantage.

Another similar antitumor drug, Opdivo, from the also American Bristol Myers Squibb, reached sales of 7,000 million euros.

By inhibiting PD-1, these drugs release the natural brakes and unleash the ferocity of T cells against cancer cells.

Japanese immunologist Tasuku Honjo won the 2018 Nobel Prize in Medicine for discovering the PD-1 protein more than a quarter of a century earlier and learning how to inhibit it to fight cancer.

The US approved the drug Keytruda in 2014 and, a year later, authorized Opdivo.

Immunotherapy was born: the stimulation of the natural defenses of the human body to try to eliminate a patient's tumor.

These treatments can cost more than 50,000 euros per year per patient in some countries.

Tasuku Honjo himself lamented these prohibitive prices in an interview with EL PAÍS in 2019. “It would be better if it were cheaper, so that everyone could benefit.

The same problem always occurs with any drug.

Even penicillin, when it hit the market, was very expensive.

And then it was affordable for anyone,” Honjo argued.

Ardolino's team already observed four years ago that these successful PD-1 inhibitor drugs, originally designed to wake up T cells, also stimulated NK cells.

The immunologist David Raulet, from the University of California at Berkeley (USA), participated in those works.

"The field of cancer immunotherapy has focused on the mobilization of T cells, but we believe that NK cells also have an important role in this movie," Raulet said at the time.

Some tumors don't respond to current treatments that activate T cells, but might succumb to an attack by spurred NK cells.

The Italian immunologist believes that his new discovery will serve to refine these therapies.

Each cancer is unique, but each person's immune system is also exceptional.

Ardolino's dream is that when a cancer patient arrives at the hospital, doctors can perform a biopsy to determine not only the specific mutations in their tumor, but also to obtain an extremely detailed profile of their immune system response.

In this way, each patient could be offered a more specific immunotherapy, even adapted to the cancerous proteins that steal their white blood cells.

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