Observation of dynamic changes in neutrophil-to-lymphocyte ratio is useful for evaluating treatment response to nivolumab in PD-L1-negative advanced oral cancer

Objective: Nivolumab is widely used for treatment of recurrent or metastatic oral squamous cell carcinoma (OSCC), but few patients benefit from this therapy. The aim of this study was to evaluate useful predictive biomarkers in OSCC patients.Methods: This study included seven patients who were diagnosed with OSCC and received nivolumab treatment more than twice at Yamanashi Central Hospital. We analyzed correlations of treatment efficacy with PD-L1 expression in the tumor microenvironment by immunohistochemistry, gene mutation profile of tumor, and neutrophil to lymphocyte ratio (NLR) in peripheral blood. Gene mutation profile was analyzed by PCR of mi-crosatellite instability and whole-exome sequencing. NLR was calculated by division of absolute neutrophil and lymphocyte counts.Results: Two patients showed complete response (CR), while five showed no therapeutic effect. PD-L1 expression was correlated with treatment efficacy in most patients, but PD-L1 expression was absent in one patient with CR. Gene mutation analysis of tumor cells did not contribute to prediction of the treatment effect in the patient, either. Pre-treatment NLR was not correlated with treatment outcome, but NLR in responders declined gradually to < 4 after the third nivolumab treatment; this markedly differed from the findings in non-responders, who exhibited increased NLR during therapy.Conclusions: NLR changes reflect the early treatment response in OSCC patients treated with nivolumab, including patients whose immune and gene mutation profiles does not correlate with treatment efficacy.