Survival in recurrent/metastatic head and neck mucosal squamous cell carcinoma (HNmSCC) remains poor. Anti-programmed death (PD)-1 therapies demonstrate improved survival albeit modest response (13-17%).
We evaluated the tumor microenvironment (TME) from advanced HNmSCC patients prior to receiving anti-PD-1 based treatment using Imaging Mass Cytometry (IMC) to develop the first detailed cellular map of the TME in advanced HNmSCC and identify hallmarks of patients most likely to benefit from anti-PD-1 therapy.
A detailed cellular interaction and region map of HNmSCC associated with response to anti-PD-1 showed increased central memory T cells and B cells in responders when compared to non-responders and 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 showed more abundant tertiary lymphoid structures (TLS) in responders, with TLS proportion >20% also associated with longer progression free survival.
We identify mechanisms of anti-PD-1 therapy response in HNmSCC patients, providing a unique opportunity to guide immunotherapy strategies and improve outcomes.