03/06/2024 - Isabelle CREMER : The heterogeneity of the lung tumor microenvironment: deciphering the role of respiratory viruses

LES LUNDIS DE SAINT-ANTOINE

Bâtiment Kourilsky - 11h–12h

Salle des Conférences (Rez de Chaussée),

184 rue du Faubourg Saint-Antoine, Paris

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LUNDI 03 JUIN 2024

The heterogeneity of the lung tumor microenvironment: deciphering the role of respiratory viruses

Isabelle CREMER

PU Sorbonne Université

invitée par Alexandre ESCARGUEIL équipe de Michèle SABBAH

(alexandre.escargueil@inserm.fr)

Non-small-cell lung cancer (NSCLC) is characterized by a poor prognosis and is distinguished by a complex and heterogeneous microenvironment (TME), the composition of which significantly influences clinical outcome and response to treatments. Besides tumor cells, the TME comprises cancer-associated fibroblasts (CAFs), endothelial cells, extracellular matrix (ECM), and subsets of immune cells organized in tertiary lymphoid structures (TLS). The heterogeneity observed in the TME is attributed to multiple factors, including genetic and epigenetic diversity, pre-existing inflammatory diseases, and the presence of microbial agents.
In our recent investigation, we have demonstrated that respiratory viral infection with Influenza A virus (IAV) reprograms the TME by acting both on immune and tumor cells. The viral infection not only accelerates tumor growth but also induces resistance to chemotherapy. Mechanistically, IAV impairs tumor-specific T cell responses, induces exhaustion of memory CD8+T cells, and induces PD-L1 expression on tumor cells. Furthermore, IAV infection modulates the transcriptomic profile of the TME towards immunosuppression, carcinogenesis, and drug metabolism.
In conclusion, our findings underscore the exacerbating impact of IAV infection on the progression of lung tumors, as it actively reshapes the TME towards a more aggressive one.
This enhanced comprehension of the intricate interplay between viral infections and the cancer microenvironment offers promising avenues for developing targeted therapeutic strategies aimed at mitigating the adverse effects of respiratory viruses on NSCLC outcomes.