Spatial mapping reveals unique cellular interactions and enhanced tertiary lymphoid structures in responders to anti-PD-1 therapy in mucosal head and neck cancers.

Ferguson, A. L.; Beddow, T.; Patrick, E.; Willie, E.; Elliott, M. S.; Low, T.-H.; Wykes, J.; Hui, M. H.; Palme, C. E.; Boyer, M.; Clark, J. R.; Lee, J. H.; Palendira, U.; Gupta, R.

doi:10.1101/2024.04.18.590189

bioRxiv · 10.1101/2024.04.18.590189

Spatial mapping reveals unique cellular interactions and enhanced tertiary lymphoid structures in responders to anti-PD-1 therapy in mucosal head and neck cancers.

Ferguson, A. L.·Beddow, T.·Patrick, E.·Willie, E.·Elliott, M. S.·Low, T.-H.·Wykes, J.·Hui, M. H.·Palme, C. E.·Boyer, M.·Clark, J. R.·Lee, J. H.·Palendira, U.·Gupta, R.

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Abstract

Survival in recurrent/metastatic head and neck mucosal squamous cell carcinoma (HNmSCC) remains poor. Anti-programmed death (PD)-1 therapies have demonstrated improved survival with lower toxicity when compared to standard chemotherapy. However, response to anti-PD-1 therapy remains modest, at 13-17%. We evaluated the tumor microenvironment (TME) using Imaging Mass Cytometry (IMC) on 27 tumor specimens from 24 advanced HNmSCC patients prior to receiving anti-PD-1 based treatment. We show significantly increased central memory T cells and B cells in responders (n=8) when compared to non-responders (n=16). Spatial mapping identified interactions between phenotypically distinct malignant squamous cells with CD8+ T cells, CD4+ Tregs and endothelial cells in responders, and avoidance of these cells in non-responders. Importantly, regional analysis shows responders have more abundant tertiary lymphoid structures (TLS), with TLS proportion >20% also associated with longer progression free survival. Together these findings define the immune landscape associated with response to anti-PD-1 treatment in HNmSCCs.

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Ferguson, A. L., Beddow, T., Patrick, E., Willie, E., Elliott, M. S., Low, T.-H., Wykes, J., Hui, M. H., Palme, C. E., Boyer, M., Clark, J. R., Lee, J. H., Palendira, U., Gupta, R.. 2024-04-21. Spatial mapping reveals unique cellular interactions and enhanced tertiary lymphoid structures in responders to anti-PD-1 therapy in mucosal head and neck cancers.. https://doi.org/10.1101/2024.04.18.590189

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