27/06/2019
Immune evasion before tumor invasion
in early lung squamous carcinogenesis
Céline Mascaux*, Mihaela Angelova*, et al… Jérôme Galon
Nature, online June 26th 2019
Understanding the largely uncharted biology of carcinogenesis requires deciphering the molecular processes in premalignant lesions and elucidating the determinants of the intralesional immune reaction during cancer development. We show that the immune response is modulated at a critical stage during carcinogenesis, so that both immune activation and evasion precede tumor invasion. We identified evolutionary trajectories of cancer and immune pathways as follow, first, a continuous increase of proliferation and DNA repair linearly form normal tissue to cancer; second, a transitory increase of metabolism and early immune sensing through activation of resident immune cells in low-grade pre-invasive lesions; third, the major activation of immune response and immune escape through immune checkpoints and suppressive interleukins from high-grade pre-invasive lesions, and fourth, the activation of the epithelial-mesenchymal transition (EMT) ultimately at the invasive stage. We propose that carcinogenesis manifests a dynamic co-evolution of the pre-invasive bronchial cells and the immune response. Our study shows that both immune activation and immune suppression occur at pre-invasive stages, which supports the hypothesis of immune surveillance in pre-cancerous lesions. These compelling findings urge the need for developing early detection immune biomarkers and immunotherapy for individuals at high risk of developing cancer.
