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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

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HNSCC.

Methods : The tumour and TIL phenotypic characteristics of 134 HNSCC specimens (HPV

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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

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The “Infiltrating” HPV

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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

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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

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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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