Programme

HPV16+ OPSCC patients display an overall longer survival and a lower recurrence rate after standard of care treatment than HPV- patients.  Because the composition of the tumor immune microenvironment (TIME) associated with good prognosis generally also predicts the success of immunotherapy, we started  to analyze an unique prospective cohort of HPV- and HPV+  OPSCC patients. We found that clinical outcome is strongly linked to the presence of HPV-specific CD4+ and CD8+ tumor infiltrating lymphocytes (TIL) during >10 years follow-up. New evidence, suggests that immunity is not only targeted at the E6 and E oncoproteins but may also involve the E2 protein. Subsequently, we performed a comprehensive multimodal, high-dimensional strategy to dissect the TIME of treatment-naïve IR+ and IR− OPSCC tissue, including bulk RNA sequencing, imaging mass cytometry and combined single-cell gene expression profiling and T-cell receptor of TIL. This revealed that IR+ tumors expressed higher levels of genes strongly related to interferon gamma signaling, T-cell activation, TCR-signaling, and mononuclear cell differentiation, as well as several immune signaling pathways, than IR− patients, specifically related to ectopic lymphoid structure development. Moreover, scRNAseq identified a subset of clonally expanded CD8+ T cells, dominantly present in IR+ tumors, which secreted T-cell and DC-attracting chemokines. Immune cell infiltration in IR+ tumors is stronger, highly coordinated, and has a distinct spatial phenotypical signature characterized by intra-tumoral microaggregates of CD8+CD103+ and CD4+ T-cells with DCs. In contrast, the IR− TIME comprised spatial interactions between lymphocytes and various immunosuppressive myeloid cell populations, which differed per patient. The impact of these results are discussed in view of our previous and current trials with (combinations of) therapeutic vaccination and checkpoint strategies.

5-slide Pitch Hans Berkhof: Preventive vaccination, also in treated OPSCC patients?
5-slide Pitch Tim Waterboer: HPV serology for screening
5-slide Pitch Ingeborg Tinhofer-Keilholz: HPV DNA assays for screening
5-slide Pitch Carole Fakhry: Positively screened for HPV: which intervention?