Exploration and therapeutic modulation of host-tumor interactions in Head and Neck carcinomas
This group belongs to the UMR 9018 - Metabolic and systemic aspects of oncogenesis for novel therapeutic approaches (Metsy)
It is increasingly clear that malignant tumors, even apparently localized, disturb the physiology of many distant organs and tissues. This systemic dimension of solid malignancies is particularly important for the tumors of the upper aero-digestive tract. Conversely, to be effective, their treatment requires a mobilization of the whole organism, notably reactivation of the immune system and nutritional restoration. Our research projects deals with these two main topics.
Carcinomas of the upper aero-digestive tract (often called “Head and Neck carcinomas” or HNCs) account for one-sixth of the world's cancer population. They pose a major public health problem in many countries, notably in France. Most are linked to alcohol and tobacco abuse but there is a viral etiological contribution for a fraction of them. Virus-related HNCs are mainly oropharyngeal carcinomas (often related to the Human Papillomavirus or HPV) and nasopharyngeal carcinomas (often related to the Epstein-Barr virus or EBV).
Our research focuses on three main areas.
1) Investigations on the immunosuppressive effects of galectin-9 (gal-9) in the tumor microenvironment and the development of neutralizing anti-gal-9 antibodies. In order to study the immunosuppressive effects of gal-9 in the tumor context in vivo, we generated isogenic murine tumor lines invalidated or not for gal-9. Recent data obtained using one of these models tend to show a suppressive effect downstream of the interferon g. It is noteworthy that galectin-9 also exerts strong immunosuppressive effects in the context of acute viral infections which reinforces the importance of our work on this protein.
2) Designing recombinant adenoviruses for new vaccine strategies with special interest for anti-HPV vaccines. The originality of our vaccine approach consists in producing adenoviral particles which are both vectors of recombinant genes and carriers of vaccine epitopes inserted into the capsid proteins. Currently, these epitopes are human papillomavirus epitopes but the same strategy can be applied to other viruses involved in acute infectious pathologies. Another research aim is to produce replicative adenoviruses combining both oncolytic and vaccine properties. Finally, a complementary project aims to improve the penetration of viral particles into cells which are poorly sensitive to viral vectors by concomitant application of an electric field.
3) The study of cellular and molecular mechanisms of muscle atrophy in patients with HNCs. Thanks to the development of reconstructive surgery, it becomes possible to collect small muscle samples which allow us to study muscle alterations in situ, especially by transcriptome analyzes (RNAseq).
Influence of soluble factors released by malignant HNC cells on the differentiation of immortalized myoblasts. Muscle differentiation was induced in human immortalized myoblasts (MyoN cells) grown in vitro for seven days in Transwell plates either (A) in the absence of co-culture or (B) subjected to indirect co-cultivation with SQ20B cells (derived from a laryngeal squamous cell carcinoma). Prior to this incubation, myoblasts were loaded with cell-permeable, low-toxicity dyes specific of nuclei (Hoechst, blue) and mitochondria (MitoTracker TM, red), respectively. The impairment of myoblast differentiation under the influence of SQ20B cells is manifested by morphological alterations like the absence of cell alignment and the low activity of mitochondria reflected by a low emission of MitoTracker TM fluorescence (scale bar : 100 mm).