Key indexes and the emerging tool for tumor microenvironment editing.

Many cancer management approaches including immunotherapies can not achieve desirable therapeutic efficacies if targeting tumors alone or could not effectively reach tumor cells. The concept of tumor microenvironment and its induced gene reprogramming have largely extended our current understandings on the determinants of tumor initiation/progression and fostered our hope in establishing first-line therapies targeting cancer microenvironment or adjuvant therapies enhancing the efficacies of existing oncotherapeutic modalities such as immunotherapies for efficient cancer management. This review identifies key indexes of tumor microenvironment, i.e., hypoxia, acidosis, hypo-nutrition and inflammation, which collectively determine the feature and the fate of adjacent tumor cells, and proposes cold atmospheric plasma, the fourth state of matter that is largely composed of various reactive oxygen and nitrogen species, as a promising tool for tumor microenvironment editing. We propose that cold atmospheric plasma represents an emerging onco-therapeutic strategy alone or complementing existing treatment approaches given its multi-modal nature through tumor microenvironment modulation.