infection with the flu virus would aggravate its evolution ⋅ Inserm, La science pour la santé

Seasonal influenza appears to promote lung tumor progression. This is indicated by the results of a study conducted in a mouse model of pulmonary adenocarcinoma. Although the molecular mechanisms involved have yet to be fully deciphered, it is already reasonable to recommend influenza vaccination to patients suffering from lung cancer and their relatives.

In patients with lung cancer, seasonal influenza is often more severe, with a higher risk of associated mortality than in the general population. To understand the links between these two diseases, one infectious and the other tumoral, the team led by Isabelle Cremer at the Cordeliers research center in Paris analyzed how the virus responsible for the flu (influenza) modulates the interactions between cancer cells and immune cells in the tumor microenvironment. This work led the researchers to observe that, at least in mice, this infection facilitates the progression of the cancerous disease: it is associated with an increase in tumor volume and a reduction in the activity of anti-tumour immune cells. In addition, it probably promotes the elimination of certain chemotherapy drugs.

An immune receptor present on tumor cells

Initially, Isabelle Cremer and her collaborators searched for the receptor that allows the influenza virus to disrupt the functioning of cells in the lungs. They were interested in TLR7: this receptor is a sentinel that specifically recognizes certain pathogens and then activates our immune defences. ” In the TLR family (for Toll-like receptors), TLR7 is the one that recognizes ARN you virus influenza. However, we have previously observed that the presence of TLR7 on the bronchial tumor cells of certain patients has a pro-tumor effect, associated with a poor prognosis and resistance to chemotherapy. We therefore wanted to know if the virus influenza could infect cancer cells and whether this infection promoted the pro-tumor effect of TRL7 », explains the researcher.

For this, the team used a mouse model of lung cancer. The researchers were able to confirm that the virus does indeed infect the tumor cells of mice, and that this infection leads to greater growth of the tumor, compared to what is observed in uninfected mice. In addition, infection has been shown to affect the efficacy of the antitumor T cell response (T cells CD8+), whose quantity and ability to react against cancer cells are then reduced. Moreover, after infection, the tumor cells begin to overexpress a protein (PDL1) which inhibits the activity of the lymphocytes supposed to lead to their destruction.

Changes that affect drug metabolism

To go further, the researchers conducted a study transcriptome “: they compared the expression of the genome of the cells of the tumor microenvironment of mice infected with the virus influenza and uninfected controls. “ We have thus identified several genes which are expressed differently following infection. Among them, some are involved in tumor growth and invasion. Others play a role in drug metabolism, suggesting that viral infection may reduce response to certain chemotherapies. »

To validate these observations in humans, Isabelle Cremer and her team analyzed transcriptomic data from patients with lung cancer, taken from a public database (The Cancer Genome Atlas Consortium – TCGA). It thus appeared that patients whose profile was close to that of mice infected with the influenza virus had a poorer prognosis: these patients strongly express genes associated with less active antitumor immunity, stronger tumor growth and greater resistance to certain chemotherapy molecules. “This result provides only indirect evidence that influenza infection can worsen the prognosis of cancer. The flu is a common illness that is not necessarily documented. Also, the data we used does not allow us to know with certainty whether these gene expression profiles are specifically linked to contact with the virus. influenzaeven though they are similar to those observed in mice after an infection “, explains Isabelle Cremer.

Reinforce information on vaccination

Future work by the team should provide more direct evidence. The researcher is helped in this by the fact that TLR7 recognizes all viruses whose genetic material consists of single-stranded RNA: the seasonal influenza virus, but also most other respiratory viruses and in particular SARS-CoV-2 responsible for Covid-19. However, the infections caused by the latter are generally well documented. ” We are currently building a bioinformatics project with other teams, to correlate the occurrence of viral infections and the transcriptomic profile of patients. We are going to work from public databases, but also from a cohort of patients followed at the Cochin Institute in Paris, operated in the thoracic surgery department directed by Marco Alifano and diagnosed in the anatomo- pathology by Diane Damotte. At the same time, Isabelle Cremer’s team is conducting tests with each of the chemotherapy molecules used in bronchial cancer: “Based on experiments carried out on bronchial tumor cells in culture, we are trying to find out whether certain drugs become inactive after viral infection. If necessary, our results will guide the treatment of patients after an episode of seasonal flu. »

While waiting to know more, the data resulting from this work calls for caution: “ It is reasonable not to neglect the flu vaccination of patients and their relatives, in order to prevent the aggravation of tumors and to maintain the activity of chemotherapy “, insists Isabelle Cremer.

Isabelle Cremer is professor of immunology at Sorbonne University, and director of the Inflammation, complement and cancer team