High-risk human papillomavirus (HPV) infection is involved in the development of anogenital cancers. To understand the immunological consequences of chronic HPV infection in pre-cancer and cancer, we used RNA-sequencing to examine transcriptomic changes that is associated with immune cell infiltration, regulatory cytokine expression and immunosuppression. This is performed using a transgenic mouse model expressing HPV E7 oncoprotein in keratinocytes, modelling skin epithelial pre-malignancy (K14E7). We observed up-regulation of transcripts encoding chemokine ligands and receptors and immune checkpoint molecules in K14E7 skin and these gene changes were validated at the protein level and can also be found to enriched in publically available microarray datasets of human CIN3 lesions. To separate the effects found in an admixture of cells from a bulk sample, we are systematically performing single-cell RNA sequencing on cells isolated from the K14E7 skin. Preliminary results from keratinocytes harvested from E7-expressing and normal control murine skin showed an interesting loss of select alarmin molecules in K14E7 keratinocytes, predicted to be during early stages of keratinocyte differentiation/stage along a pseudo-time scale. This suggests that alarmin suppression may be a mechanism by which E7-expressing cells avoid immune surveillance and interfere with effector T cell function. Taken together, the data is supporting the overall hypothesis that HPV-associated hyperproliferative epithelium induces stress signals and expresses chemokine signals to drive immune cell infiltrate into this environment but at the same time, preferentially suppress expression of epithelial damage signals.

Bio

Dr. Hang Ta is a NHMRC ECR Fellow at Australian Institute for Bioengineering and Nanotechnology, the University of Queensland.  She got her Bachelor degree in Chemical Engineering (Vietnam), a Masters degree in Biotechnology (UQ) and a PhD in Drug Delivery (Melbourne Uni). During her research career, she has been awarded a number of prizes, small grants and prestigious fellowships such as National Heart Foundation and NHMRC ECR fellowships. Her research addresses solutions for current problems in diagnosis and treatment of diseases. Research interests: nanomaterials for cardiovascular disease, cancerous diseases and blood disorder diseases.

 

This seminar will be followed by: 19F MRI Agents: from Fundamental Designs to Biological Applications

About AIBN Seminar Series

The AIBN Seminar series showcases a range of seminars across different topics and disciplines

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AIBN Seminar Room