Following T-cell activation, HPV-associated HNSCC develops a negative feedback loop to forge an immunosuppressive microenvironment with upregulated expression of CTLA4 [23], CD39 and multiple T-cell exhaustion markers including LAG3, PD1, TIGIT and TIM3 [24], as per transcriptome data from TCGA. This evidence concerns the gene PDCD1 and head and neck squamous cell carcinoma.