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Cold atmospheric plasma sensitizes head and neck cancer to chemotherapy and immune checkpoint blockade therapy

Yanhong WangDepartment of ORL-HNS, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai, 200432, ChinaXinyu MangDepartment of Biochemistry and Molecular Biology, State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, 100005, ChinaDanni LiDepartment of ORL-HNS, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai, 200432, ChinaZhao WangDepartment of ORL-HNS, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai, 200432, ChinaY ChenDepartment of Biochemistry and Molecular Biology, School of Medicine, Tongji University, Shanghai, 200072, ChinaZhenyu CaiDepartment of Biochemistry and Molecular Biology, School of Medicine, Tongji University, Shanghai, 200072, ChinaFei TanDepartment of ORL-HNS, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai, 200432, China; The Royal College of Surgeons in Ireland, Dublin, Ireland; The Royal College of Surgeons of England, London, UK. Electronic address: [email protected]

2023en

ABI

Annotatsiya

Head and neck cancer (HNC) is the seventh most prevalent cancer globally, often characterized by chemo-resistance and immunosuppression, which significantly hampers treatment efficacy. Cold atmospheric plasma (CAP) has recently emerged as a promising adjuvant oncotherapy with substantial potential and advantages. In this study, Piezobrush® PZ2, a handheld CAP unit based on the piezoelectric direct discharge technology, was used to generate and deliver non-thermal plasma. We aimed to investigate the effects of CAPPZ2 on various types of HNC cells and elucidate the underlying mechanisms. In addition, we endeavored to examine the efficacy of combining CAPPZ2 with chemotherapy drugs (i.e., cisplatin) or immune checkpoint blockade (ICB, i.e., PD1 antibody) in HNC treatment. Firstly, the results demonstrated that CAPPZ2 exerted anti-neoplastic functions through inhibiting cell proliferation, migration and invasion, and promoting apoptosis and autophagy. Secondly, using transcriptomic sequencing, Western blotting, and quantitative real-time PCR, the mechanisms underlying CAPPZ2 treatment in vitro was presumed to be a multitargeted blockade of major cancer survival pathways, such as redox balance, glycolysis, and PI3K/AKT/mTOR/HIF-1α signaling. Lastly, combinatorial thearpy containing CAPPZ2 and cisplatin or PD-1 antibody significantly suppressed tumor growth and prolonged recipient survival in vivo. Collectively, the synergistic effects of CAPPZ2 and cisplatin or PD-1 antibody could serve as a promising solution to enhance head and neck tumor elimination.

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Identifikatorlar

DOI: 10.1016/j.redox.2023.102991

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