Tumours infiltration by CD8 T cells is linked to favourable outcomes in several cancers. However, chronic activation of T-cells leads to up-regulation of PD-1 that on interaction with its ligand PD-L1 can modulate effector function. Importantly, blocking antibodies to PD-1 or its ligand have shown efficacy in treatment of some cancers. Expression of PD-L1 in the tumour microenvironment could therefore be a biomarker of potential response to checkpoint inhibitors.
Here, the densities of T cells, macrophages and their PD-1 and PD-L1 expression are assessed within different tumour microenvironments by multiplex immune-fluorescent labelling in 124 OPSCC and association with HPV status and clinical outcomes evaluated.
In HPV+ OPSCC patients CD8 density in the stroma correlates with significantly improved survival. By contrast, HPV- OPSCCs have a lower CD8 infiltration and a higher proportion of PD-1+ CD8 T cells and PD-L1+CD68 macrophages in their stroma. These data are consistent with checkpoint modulation leading to poorer clinical outcome in HPV- patients. However within this group, the infiltration of CD68 especially PD-L1+CD68 cells and increased expression of PD-L1 in the stroma are all associated with significantly improved survival. This implies the best control of HPV- tumours is driven by macrophage activity.
CD8 T cell and CD68 PD-L1+ macrophage densities differ between HPV+ and negative OPSCC and are associated with differing outcomes. This may reflect a different natural history with altered immune control mechanisms apparent in the cancers at time of diagnosis. No simple pattern of PD-L1 expression is utilizable as a biomarker for either prognosis or treatment selection in OPSCC.