Malignant melanoma is a devastating disease.,Because of its aggressiveness, it also serves as a model tumor for investigating novel therapeutic avenues.,In recent years, scientific evidence has shown that cold atmospheric plasma (CAP) might be a promising modality in cancer therapy.,In this study, we aimed to evaluate the effect of CAP generated by an argon plasma jet alone or in combination with dacarbazine (DAC) on melanoma cells in vitro and in vivo.,The effects of the CAP on inducing lipid peroxidation and nitric oxide production were higher in B16 melanoma cells in comparison to non-malignant L929 cells.,Assays on cell growth, apoptosis, and expression of genes related to, e.g., autophagic processes, showed CAP to have a substantial impact in melanoma cells while there were only minoreffects in L929 cells.,In vivo, both CAP monotherapy and combination with DAC significantly decreased tumor growth.,These results suggest that CAP not only selectively induces cell death in melanoma but also holds promises in combination with chemotherapy that might lead to improved tumor control.
Immunotherapy has revolutionized cancer treatment, yielding unprecedented long-term responses and survival.,However, a significant proportion of patients remain refractory, which correlates with the absence of immune-infiltrated (“hot”) tumors.,Here, we observed that FDA-approved unadjuvanted seasonal influenza vaccines administered via intratumoral injection not only provide protection against active influenza virus lung infection, but also reduce tumor growth by increasing antitumor CD8+ T cells and decreasing regulatory B cells within the tumor.,Ultimately, intratumoral unadjuvanted seasonal influenza vaccine converts immunologically inactive “cold” tumors to “hot,” generates systemic responses, and sensitizes resistant tumors to checkpoint blockade.,Repurposing the “flu shot” may increase response rates to immunotherapy, and based on its current FDA approval and safety profile, may be quickly translated for clinical care.,Reprogramming the tumor microenvironment to increase immune-mediated responses is currently of intense interest.,Patients with immune-infiltrated “hot” tumors demonstrate higher treatment response rates and improved survival.,However, only the minority of tumors are hot, and a limited proportion of patients benefit from immunotherapies.,Innovative approaches that make tumors hot can have immediate impact particularly if they repurpose drugs with additional cancer-unrelated benefits.,The seasonal influenza vaccine is recommended for all persons over 6 mo without prohibitive contraindications, including most cancer patients.,Here, we report that unadjuvanted seasonal influenza vaccination via intratumoral, but not intramuscular, injection converts “cold” tumors to hot, generates systemic CD8+ T cell-mediated antitumor immunity, and sensitizes resistant tumors to checkpoint blockade.,Importantly, intratumoral vaccination also provides protection against subsequent active influenza virus lung infection.,Surprisingly, a squalene-based adjuvanted vaccine maintains intratumoral regulatory B cells and fails to improve antitumor responses, even while protecting against active influenza virus lung infection.,Adjuvant removal, B cell depletion, or IL-10 blockade recovers its antitumor effectiveness.,Our findings propose that antipathogen vaccines may be utilized for both infection prevention and repurposing as a cancer immunotherapy.