Johanne Audouze-Chaud

Since Oct 2023:
PhD student, Immunotherapy and Immunoprevention, DKFZ, Heidelberg

2021 - 2023
MSc Applied Immunology, University of Toronto

2018 - 2021
BSc Life Sciences with Major in Molecular and Cell Biology, Strasbourg University
BSc Human and Molecular Biology, Saarland University

Multi-omics analysis of the effects of combining therapeutic vaccination with low-dose irradiation for the treatment of orthotopic HPV-driven cancers

Cervical cancer, other anogenital cancers and a subset of head and neck cancers are caused by persistent infection with high-risk human papillomaviruses (HPV). Current research focuses on the development of targeted immunotherapies for HPV-driven cancers, including therapeutic vaccination. Our group validated several promising HLA-restricted target epitopes derived from the HPV16 E6 and E7 oncoproteins and developed a peptide-based vaccine targeting the lead epitope HPV16 E7/11-19.
Previous experiments already demonstrated therapeutic potential of the vaccine in subcutaneous tumors. However, one of the major hurdles of therapeutic vaccination is to direct the induced antigen-specific T cells to the correct tumor site. Therefore, we established a novel HPV16 tumor model in MHC-humanized A2.DR1 mice. The cancer cells are immortalized by and thus dependent on the HPV16 oncogenes E6 and E7, and present "human", i.e. HLA-restricted HPV epitopes. We established orthotopic tumors at two biologically relevant anatomical sites, namely the female genital tract and the base of the tongue, modelling the situation in human patients.
Low dose irradiation was shown to promote tumor immunogenicity and immunotherapy responses. The aim of the current project is therefore to assess the impact of low-dose X-ray irradiation on the tumor microenvironment (TME), especially the tumor immune microenvironment (TIME), in our tumor models. This will be done by a combination of several methodologies (scRNAseq, spatial omics, histology, immunofluorescence, (spectral) flow cytometry, in vivo imaging). Depending on the results, a combination regimen with our therapeutic vaccine will be devised. Treatment efficacy will be assessed by tumor regression (luminescence intensity and MRI-based volumetry), T cell activation (spectral flow cytometry) and immune infiltration (multiplex immunofluorescence). The proposed experiments will first be applied to the oropharyngeal tumor model, and can also be carried out in the genital tumor model.
Taken together, these experiments will be a crucial step in the preclinical assessment of new therapeutic HPV vaccine combination treatment strategies to effectively combat mucosal tumors. The obtained results will provide important insights for the design of upcoming clinical trials.