The coronavirus pandemic has been a masterclass in understanding that each person has distinctive defenses against disease. Some infected people didn't even notice it and others died within a few 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 drivers of this variability. They recruited 1,000 healthy people between the ages of 20 and 70 in the French city of Rennes and selected 100 volunteers of each gender for each decade. They all provided blood and stool samples and completed a 44-page questionnaire about their lifestyle. They even took skin biopsies to grow their cells in the lab. This Wednesday the latest results will be presented: Smoking is the factor that most alters the immune system, even years after you have stopped smoking.
According to a World Health Organization count, there are more than 100 reasons to give up tobacco: the increased risk of developing cancer or a heart attack, bad body odor, the cost (more than 1,800 euros a year for a pack of daily smokers), wrinkles on the face, yellow Teeth, damage in people exposed to passive smoking. Reasons 79, 80, 81 and 82 state 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 today 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 greatest impact of the 136 factors analyzed, followed by body mass index and latent infections caused by cytomegalovirus, a pathogen known to leave consequences in one in five affected babies.
The study's authors from the Pasteur Institute in Paris focused on the production of cytokines, proteins released in cells when they recognize a pathogen and help coordinate the immune response. Researchers led by biologist Violaine Saint-André and immunologist Darragh Duffy have observed that smoking impairs the non-specific defenses we are born with and triggers stronger inflammatory reactions. This harmful effect disappears when you stop smoking. However, scientists have found that the cells responsible for the specific immunity acquired throughout life remain altered for years after quitting smoking. Smoking is the only element whose effects are comparable to immutable factors such as age, gender and genetics.
The Spanish biologist Lluís Quintana-Murci (front row, middle) with his team from the Pasteur Institute. Pasteur Institute
The researchers defend that their findings “have potential clinical implications for the risk of developing infections, cancer and autoimmune diseases,” but are cautious. They have not yet studied the connection between this change in white blood cells and tumors. “However, it is known from many other previous works that smoking increases the risk of several types of cancer. However, 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 that observed a 50 percent reduction in cancer risk after 15 years of quitting smoking.
The 1,000 volunteers in Rennes have Western European ancestry to facilitate analysis in a genetically homogeneous population, but the authors are already working on similar experiments in other places such as Senegal and Hong Kong. Lluís Quintana-Murci, born 53 years ago in Palma de Mallorca, has been working in Paris for more than two decades.
The president of the Spanish Society of Immunology, Marcos Lopez Hoyos, praises the new work, in which he was not involved. “In many patients with chronic smoking and COPD [enfermedad pulmonar obstructiva crónica] We always saw one clinical finding: we found hypogammaglobulinemia [bajos niveles de anticuerpos], which is a cause of secondary immune deficiency,” he emphasizes. “With COPD with smoking, there are more infections and more cancer. The change in cytokines they observed clearly indicates that it can favor a change in the regulation of the immune response and cause these diseases, even if they do not prove it,” says López Hoyos, scientific director of the Marqués de Valdecilla Research Institute, in Santander. “It’s a wonderful experiment,” he enthuses.
The new results are “very interesting but not surprising,” said oncologist Alberto Ocaña, who stressed his caution. “The study only shows that tobacco changes the immune system, not that these changes are the cause of cancer. Cancer is a genetic disease that also requires other additional changes, such as a dysfunctional immune system,” explains Ocaña, coordinator of the Department of Experimental Cancer Therapies at the San Carlos Clinical Hospital in Madrid.
The team at the Pasteur Institute cultured cells from volunteers, exposed them to various substances in the laboratory and analyzed how they behaved. Immunologist África González from the University of Vigo is surprised by the duration of the effects of smoking. “It's striking that this signature is permanently retained in the immune system, as if to say: 'You smoked.' And when these cells were exposed to tobacco, they behave differently towards a pathogen,” he reflects. “You cannot say categorically that this change increases the risk of cancer, but tobacco itself not only alters the immune response, but also contains many substances that are carcinogenic in themselves,” warns González.
You can follow THEME on Facebook, X and Instagram, or sign up here to receive our weekly newsletter.