The coronavirus pandemic was a master class in understanding that each person has characteristic defenses once morest diseases. Some infected did not even realize it and others died in a matter of days. A little over a decade ago, Spanish biologist Lluís Quintana-Murci and his American colleague Matthew Albert began a bold experiment to understand the determining factors of this variability. They recruited 1,000 healthy people between 20 and 70 years old in the French city of Rennes, choosing 100 volunteers of each sex for each decade. They all provided blood and stool samples and filled out a 44-page questionnaire regarding their lifestyle. Skin biopsies were even taken to grow their cells in the laboratory. The latest results are presented this Wednesday: smoking is the factor that most alters defenses, even years following having stopped smoking.
There are more than 100 reasons to reject tobacco, according to the count of the World Health Organization: the greater risk of suffering from cancer or a heart attack, bad body odor, the expense (more than 1,800 euros a year for pack-a-day smokers), wrinkles on the face, yellow teeth, damage to people exposed to second-hand smoke. Reasons 79, 80, 81 and 82 detail that the toxic substances in tobacco weaken the immune system and increase the risk of infections, tumors, autoimmune diseases and AIDS. The new study, published this Wednesday in the journal Nature, warns that the white blood cells of ex-smokers remain altered for years. It is the environmental factor that has the most influence of the 136 analyzed, followed by body mass index and latent infections by cytomegalovirus, a pathogen known to leave consequences in one in five affected babies.
The authors of the study, from the Pasteur Institute in Paris, have focused on the production of cytokines, proteins that are released in cells when they detect a pathogen and help coordinate the immune response. The researchers, led by biologist Violaine Saint-André and immunologist Darragh Duffy, have observed that smoking affects the non-specific defenses with which we are born, causing greater inflammatory responses. This harmful effect disappears when you stop smoking. However, scientists have detected that the cells responsible for specific immunity – acquired during life – do remain altered for years following stopping smoking. Smoking is the only element with effects comparable to immutable factors such as age, sex and genetics.
The researchers defend that their results “have potential clinical implications on the risk of developing infections, cancer and autoimmune diseases,” but they are cautious. They have not yet studied the relationship between this alteration of white blood cells and tumors. “However, it is well known from much other previous work that smoking increases the risk of multiple types of cancer, but the longer it has been since you stopped smoking, the lower the risk,” explains Duffy. The immunologist cites a recent study, with almost three million participants in South Korea, which has observed a 50% reduction in the risk of cancer following 15 years of quitting smoking.
The 1,000 volunteers in Rennes have Western European ancestors, to facilitate analysis in a genetically homogeneous population, but the authors are already working on similar experiments in other locations, such as Senegal and Hong Kong. Lluís Quintana-Murci, born in Palma de Mallorca 53 years ago, has worked in Paris for more than two decades.
The president of the Spanish Society of Immunology, Marcos Lopez Hoyos, applauds the new work, in which he has not participated. “In many patients with chronic smoking and COPD [enfermedad pulmonar obstructiva crónica] we have always seen a clinical finding: we found hypogammaglobulinemia [bajos niveles de anticuerpos], which is a cause of secondary immunodeficiency,” he points out. “In COPD with smoking there are more infections and there is more cancer. The alteration of the cytokines that they have observed clearly indicates that it can favor an alteration in the regulation of the immune response and generate these diseases, although they do not prove it,” says López Hoyos, scientific director of the Marqués de Valdecilla Research Institute, in Santander. “It’s a beautiful experiment,” he celebrates.
The new results are “very interesting, but not surprising,” according to oncologist Alberto Ocaña, who emphasizes his caution. “The study only shows that tobacco alters the immune system, not that these alterations are the cause of cancer. Cancer is a genetic disease that also requires other added alterations, such as a dysfunctional immune system,” explains Ocaña, coordinator of the Experimental Cancer Therapies Unit at the San Carlos Clinical Hospital, in Madrid.
The Pasteur Institute team has grown cells from volunteers, put them in contact with different substances in the laboratory and analyzed how they behave. Immunologist África González, from the University of Vigo, is surprised by the duration of the effect of smoking. She “It is striking that this signature is persistently maintained in the immune system, as if saying: ‘You have smoked.’ And those cells, when they have been exposed to tobacco, are going to behave differently in the face of a pathogen,” she reflects. “They cannot say categorically that this alteration increases your risk of cancer, but tobacco itself not only alters the immune response, but also has many substances that are carcinogenic in themselves,” warns González.
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