UVC-Induced Oxidative Stress and DNA Damage Repair Status in Head and Neck Squamous Cell Carcinoma Patients with Different Responses to Nivolumab Therapy

Accumulation of evidence highlights the crosstalk between the DNA damage repair and the immune system. Herein, we tested the hypothesis that in Head and Neck Squamous Cell Carcinoma (HNSCC), DNA repair capacity of patients’ PBMCs correlates with therapeutic response to immune checkpoint blockade. Following in vitro UVC irradiation, oxidative stress, apurinic/apyrimidinic (AP) lesions, endogenous/baseline DNA damage and DNA damage repair efficiency were evaluated in three HNSCC (UM-SCC-11A, Cal-33, BB49) and two normal cell lines (RPMI-1788, 1BR-3h-T), as well as in peripheral blood mononuclear cells (PBMCs) from 15 healthy controls (HC) and 49 recurrent/metastatic HNSCC patients at baseline (8 responders, 41 non-responders to subsequent nivolumab therapy). HNSCC cell lines showed lower DNA repair efficiency, increased oxidative stress and higher AP-sites than normal ones (all P < 0.001). Moreover, patients’ PBMCs exhibited increased endogenous/baseline DNA damage, decreased DNA repair capacity, augmented oxidative stress and higher AP-sites than PBMCs from HC (all P < 0.001). Importantly, PBMCs from responders to nivolumab therapy showed lower endogenous/baseline DNA damage, higher DNA repair capacities, decreased oxidative stress and reduced AP-sites than non-responders (all P < 0.05). Together, we demonstrate that oxidative stress status and DNA repair efficiency evaluated in PBMCs from HNSCC patients correlate with response to immune checkpoint blockade.