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Fewer tumour-specific PD-1+CD8+ TILs in high-risk “Infiltrating” HPV− HNSCC

Menée à partir de données portant sur des échantillons de carcinome épidermoïde de la tête et du cou et menée à l'aide d'un modèle murin, cette étude met en évidence, par rapport aux tumeurs infectées par le papillomavirus humain, la présence d'une moins grande quantité de lymphocytes T CD8+ PD-1+ dans les tumeurs non infectées par ce virus

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 CD8

α, 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.

British Journal of Cancer , résumé, 2020

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