Fewer tumour-specific PD-1 + CD8 + TILs in high-risk "Infiltrating" HPV - HNSCC.

BACKGROUND: The prognosis of HPV- HNSCC was worse than that of HPV+ HNSCC. Analysis of tumours and tumour-infiltrating lymphocytes (TILs) may provide insight into the progression of HPV- HNSCC.

METHODS: The tumour and TIL phenotypic characteristics of 134 HNSCC specimens (HPV- tumours were classified into "Infiltrating" and "Pushing" subtypes based on their different tumour nest configuration and prognosis) were retrospectively analysed. HNSCC data from the Cancer Genome Atlas (n = 263) were analysed for CD8α, HPV and overall survival (OS). A murine HNSCC model was used to verify the antitumour role of PD-1+ CD8+ TILs.

RESULTS: The "Infiltrating" HPV- subtype showed shorter OS than the "Pushing" subtype. Moreover, there is a tendency from "Pushing" to "Infiltrating" subtype from the primary to the recurrent lesion. Different from total CD8+ TILs, tumour-specific PD-1+ CD8+ TILs were fewer in invasive margin (IM) of "Infiltrating" HPV- tumours. PD-1+ CD8+ TILs recognised autologous HNSCC cells and showed stronger inhibition of tumour growth in a murine HNSCC model resistant to PD-1 blockade.

CONCLUSIONS: Coevolution of HPV- HNSCC and TILs is characterised by an "Infiltrating" phenotype and less tumour-specific PD-1+ CD8+ TILs, which may provide a framework for further translational studies and patient stratification.