British journal of cancer · 2025
Association of DNA damage response signals and oxidative stress status with nivolumab efficacy in patients with Head and Neck Squamous Cell Carcinoma.
СтатьяКлиническое исследование II фазыНазвание и аннотация: Перевод пока не подготовлен
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Papanikolaou Christina, Economopoulou Panagiota, Spathis Aris, Kotsantis Ioannis, Gavrielatou Niki, Anastasiou Maria, Moutafi Myrto, Kyriazoglou Anastasios, Foukas George-Romanos P, Lelegiannis Ioannis M, Rimm David, Panayiotides Ioannis, Foukas Periklis, Souliotis Vassilis L, Psyrri Amanda
Аннотация
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.
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.