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

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. ### Competing Interest Statement Conflicts of interest: JHL declares Honorarium from MSD, BMS, AstraZeneca, Conference support from Novartis, Advisory Board MSD, Sanofi.