Influenza as a “coach” in the fight against cancer

Every day, people “quietly” protect themselves from harmful microorganisms. These battles that we are winning – often unintentionally – are the result of a long history of coexistence and evolution with numerous pathogens. Exposure to them taught our immune system to recognize infection, fight it and prevent disease.

Encountering infectious agents is one of the stimuli that strengthens our defensive capacity, sometimes beyond what we imagine. And an example is what happens when the body fights the flu.

immune training

Influenza is a disease caused by four types of viruses belonging to the family Orthomyxoviruses, which are classified according to the characteristics of their genome. Humans are primarily affected by influenza A and B viruses.

Despite their deadly risk, facing these viruses and defeating the disease can have a positive effect.

Self-treatment for the flu can be compared to doing a training session that helps us pass a certain test and learn how to better overcome it in the future. But it will also train our immune systems to deal with similar threats, like other flu viruses, and completely different ones, like other respiratory viruses or even cancer.

Training our defenses in a non-specific way is a concept that has been known for a long time, but what determines its activation and its effects is currently the subject of study.

Bookmark in DNA

The immune system can be divided into two large groups: adaptive and innate. Through inoculation, we preferentially educate the former. Instead, to train the innate system, it is necessary to activate its constituent cells or its precursors: monocytes, NK cells, macrophages, innate lymphoid cells, dendritic cells, and neutrophils. The instruction of these cells is converted into innate immune memory or trained immunity.

Microbial substances or compounds produced by our cells during infection can stimulate the innate immune system to respond to what is perceived as aggression by expressing certain genes. This stimulus leaves a mark on the DNA, as if it were a bookmark in a book we had previously read.

“Markers” are produced in the form of methylation in the DNA of innate immune cells and modifications of histones, the proteins that package this DNA. They act as markers for more efficient detection of certain genes in case our innate immune cells are stimulated again.

This labeling may promote a faster and more effective response to future infections, but it may also cause an excessive inflammatory response with detrimental consequences.

Antitumor effects of past influenza (in mice)

Recently published journal article Nature described the process of trained immunity caused by infection. The researchers inoculated mice with a non-lethal influenza virus. One month after recovery from the infection, the animals were treated for lung tumors.

And surprisingly, the mice that recovered from the flu developed tumors more slowly than those that had not been infected beforehand.

The best antitumor protection is provided by the stimulation of trained immunity of a type of cell called alveolar macrophages. These cells are responsible for clearing and eliminating particles or microorganisms that enter our lungs when we breathe and control the inflammation that occurs when a foreign agent is recognized.

During an acute infection, many alveolar macrophages die, but we regenerate them later. This recovery is marked by the presence of “markers” in some inflammatory genes.

The training of these macrophages depends on other partners, NK cells. They act as trainers during influenza virus infection by producing a cytokine (a protein that regulates the immune response) called interferon gamma.

This cytokine is similar to Fierabrás balm for alveolar macrophages: it stimulates their ability to engulf and digest tumor cells, which can also increase the activation of the adaptive immune response.

This discovery is not a short-term solution for treating lung cancer or tumors in general. However, the focus is on two ideas that could revolutionize the treatment of some tumors: viruses with oncolytic immunostimulatory activity that can activate the immune system to selectively kill tumor cells, and stimulation of innate antitumor immunity.

In the 1950s and 1960s, Alice Moore, MD, pioneered the study of oncolytic viruses in animal models. We are at the dawn of its use by the human immune system to specifically attack and destroy tumor cells. In this challenge lies the next frontier of anticancer immunotherapy.

Estanislao Nistal Villan, Virologist and Professor of Microbiology, Faculty of Pharmacy, CEU San Pablo University and Sarah Cuadrado Castaño, PhD, Associate Research Professor, Icahn School of Medicine at Mount Sinai

This article was originally published on The Conversation. Read the original.