Gene-expression profiling on a HPV-related head and neck cancer patient with idiopathic CD4 lymphocytopenia and complete remission to checkpoint inhibitors

PD-L1 immunohistochemical staining has been not always enough reliable to accurately predict the response to immunotherapy; thus, and other biomarkers are required. In this context qualitative and quantitative multiparametric analyses seems promising. Data on the activity of nivolumab in challenging populations (e.g patients with autoimmune disorders; post-organ transplant; chronic viral infections; ongoing immunosuppressant use; elderly) are scant, mainly due to their underrepresentation in clinical trials. Nonetheless, it has been demonstrated that the use of ICI is safe and effective in HIV oncologic patients. Herein, we analyzed a metastatic HNSCC patient with an idiopathic CD4 lymphocytopenia who, after a recovery from a progressive multifocal leukoencephalopaty received 10 courses of nivolumab and obtained a complete remission maintaining the response two years after PD-1 blockade withdrawn. A 64 year-old man, active smoker, was referred to the Fondazione IRCCS Istituto Nazionale Tumori (Milan, Italy). A contrast head and neck MRI demonstrated a large lesion of the right infratemporal fossa. Fine needle aspiration biopsy of the largest neck node (25 mm) demonstrated a poorly differentiated carcinoma. Tumor was staged as an oropharynx cancer, p16 positive, high-risk HPV-DNA positive, cT4 N1 according to AJCC VIII classification. Immunohistochemical analysis showed high PD-L1 expression both in tumour cells (40%) and infiltrating cells (20%) with a CPS of 60. Moreover, we observed an enrichment (80%) of tumor-infiltrating lymphocytes (TILs). RNA was extracted from 10 frozen blood buffycoat (QIAGEN RNeasy Lipid Tissue Mini Kik,Qiagen): 5 samples were collected from the “case” patient; 5 samples were collected from 5 HNSCC patients tumor-free after first line treatment, used as “controls”.