Gas plasma-induced bacterial PAMP release promotes skin cancer cell death

Infected skin tumors are challenging to treat and frequently result in tumor progression, relapses, and post-surgical complications. Moreover, bacterial infections significantly contribute to tumor therapy resistance as they release tumor microenvironment (TME)-modulating molecules. Immune or cancer cells can recognize these pathogen-associated molecular patterns (PAMPs), initiating signaling and pro- or antitumoral response. Hence, understanding PAMPs in tumor therapy may improve the understanding and efficacy of cancer treatment. Cold gas plasma treatment has shown promise in treating infected, ulcerative head and neck cancers. Here, we elucidated gas plasma-induced bacterial PAMP release and their combination with direct gas plasma exposure in skin cancer cells in vitro. Evaluating metabolic activity and viability of tumor cells revealed a significantly stronger growth-inhibitory effect of the combinatory treatment, suggesting a relevant contribution of bacterial molecules to tumor toxicity. A synergistic effect was found regarding the oxidative damage marker γH2AX that was elevated in response to the combination treatment. Cancer cells subjected to gas plasma and provoked PAMPs exhibited an altered phenotype that displayed a strikingly different chemokine and cytokine profile. Mass spectrometry analysis showed improved bacterial cell lysis by gas plasma treatment, increasing intracellular protein release of all three tested bacterial strains.