Association of DNA damage response signals and oxidative stress status with nivolumab efficacy in patients with Head and Neck Squamous Cell Carcinoma

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Abstract
Background Accumulating evidence suggests that deregulation of DNA damage response (DDR) network affects multiple aspects of the immune system. Herein, we tested the hypothesis that DDR-related signals, measured in peripheral blood mononuclear cells (PBMCs) from Head and Neck Squamous Cell Carcinoma (HNSCC) patients, correlate with the response to immune checkpoint inhibitors. Methods Oxidative stress and DDR-related signals were evaluated in PBMCs from 26 healthy controls and 50 recurrent/metastatic HNSCC patients at baseline, who participated in a phase II nivolumab trial (NCT03652142). Spatial transcriptomics in three molecularly defined tissue compartments (tumour, leucocyte, macrophage) from biopsies of overlapping cases were also investigated. Results PBMCs from responders to nivolumab therapy showed significantly lower oxidative stress, endogenous DNA damage, DNA repair capacities and apoptosis rates compared with non-responders (all P < 0.04). The analysis of tissue RNA in situ data illustrated that DNA repair pathways showed enrichment in the macrophage compartment of baseline tissue biopsies of responders compared with non-responders (P = 0.049). Conclusions Our findings demonstrate that oxidative stress and deregulated DDR-related signals measured in PBMCs from HNSCC patients at baseline correlate with response to nivolumab and, if further validated, may be exploited as novel non-invasive biomarkers and the design of clinical trials.
Funding Information
  • Hellenic Society of Medical Oncology (N/A)

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