CC BY 4.0 UnportedWitzke, KatharinaSeebauer, ChristianJesse, KatjaKwiatek, ElisaBerner, JuliaSemmler, Marie‐LuiseBoeckmann, LarsEmmert, SteffenWeltmann, Klaus‐DieterMetelmann, Hans‐RobertBekeschus, Sander2021-12-102021-12-102020https://oa.tib.eu/renate/handle/123456789/7666https://doi.org/10.34657/6713The prognosis of patients suffering from advanced-stage head and neck squamous cell carcinoma (HNSCC) remains poor. Medical gas plasma therapy receives growing attention as a novel anticancer modality. Our recent prospective observational study on HNSCC patients suffering from contaminated tumor ulcerations without lasting remission after first-line anticancer therapy showed remarkable efficacy of gas plasma treatment, with the ulcerated tumor surface decreasing by up to 80%. However, tumor growth relapsed, and this biphasic response may be a consequence of immunological and molecular changes in the tumor microenvironment that could be caused by (a) immunosuppression, (b) tumor cell adaption, (c) loss of microbe-induced immunostimulation, and/or (d) stromal cell adaption. These considerations may be vital for the design of clinical plasma trials in the future.enghttps://creativecommons.org/licenses/by/4.0/530540cold physical plasmaHNSCCkINPenplasma medicinetumor microenvironmentArticle