Cold atmospheric plasma: Novel opportunities for tumor microenvironment targeting

With mounting preclinical and clinical evidences on the prominent roles of the tumor microenvironment (TME) played during carcinogenesis, the TME has been recognized and used as an important onco-therapeutic target during the past decade. Delineating our current knowledge on TME components and their functionalities can help us recognize novel onco-therapeutic opportunities and establish treatment modalities towards desirable anti-cancer outcome. By identifying and focusing on primary cellular components in the TME, that is, tumor-infiltrating lymphocytes, tumor-associated macrophages, cancer-associated fibroblasts and mesenchymal stem cells, we decomposed their primary functionalities during carcinogenesis, categorized current therapeutic approaches utilizing traits of these components, and forecasted possible benefits that cold atmospheric plasma, a redox modulating tool with selectivity against cancer cells, may convey by targeting the TME. Our insights may open a novel therapeutic avenue for cancer control taking advantages of redox homeostasis and immunostasis.