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.