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Institution: Centre for Cancer Biology, University of South Australia - South Australia, Australia
Head and neck squamous cell carcinoma (HNSCC) are highly heterogeneous, biologically aggressive and invasive malignancies that cause more than 450,000 deaths globally each year. Enhancing T cell responses to HNSCC has significant promise to improve outcomes, as T cells are associated with better prognosis, and boosting their activity with immunotherapies targeting PD-1 can improve survival in recurrent or metastatic HNSCC. However, the vast majority of patients either do not respond, are ineligible for treatment, or are unable to withstand treatment toxicity. Thus, there is an urgent and critical unmet clinical need to develop new strategies to enhance anti-HNSCC host T cell responses.
Using state-of-the-art spatial gene expression profiling of HNSCC whole-tissue samples from our patient registry, we have identified a new axis of anti-tumour T cell regulation mediated by intratumoural eosinophils, a type of innate immune cell. Eosinophils were enriched in advanced HNSCC tumours, where they formed close interactions with dysfunctional T cells. In mouse models of oral SCC, eosinophils infiltrated into tumours and were able to suppress tumour growth. This unexpected discovery opens a new avenue to understand the mechanisms of immune dysfunction in cancer and provides a new pathway to develop improved immunotherapies for this poor prognostic cohort.
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Dr Carly Whyte - , Dr Laura Kenyon - , Dr Damon Tumes - , Prof Harshita Pant -