Modulation of the Tumor-Associated Immuno-Environment by Non-Invasive Physical Plasma

SIMPLE SUMMARY: Non-invasive physical plasma can be used in various medical applications. As the name suggests, this treatment is non-invasive, as the plasma device is placed over the area to be treated and cold plasma is applied. The main effect of plasma treatment is achieved by reactive oxygen and reactive nitrogen species which induce oxidative stress in the treated sample. Cancer cells are very sensitive to non-invasive physical plasma and plasma treatment induces apoptotic and immunogenic cell death of cancer cells. In the latter, dying cancer cells send out so-called “eat-me” signals which recruit and activate specific immune cells. Non-invasive physical plasma can also directly activate immune cells and increase their aggressiveness (cytotoxicity) towards cancer cells. In addition to cancer and immune cells, plasma treatment affects other parts of the tumor, such as the vasculature, and generally leads to reduced tumor growth. ABSTRACT: Over the past 15 years, investigating the efficacy of non-invasive physical plasma (NIPP) in cancer treatment as a safe oxidative stress inducer has become an active area of research. So far, most studies focused on the NIPP-induced apoptotic death of tumor cells. However, whether NIPP plays a role in the anti-tumor immune responses need to be deciphered in detail. In this review, we summarized the current knowledge of the potential effects of NIPP on immune cells, tumor–immune interactions, and the immunosuppressive tumor microenvironment. In general, relying on their inherent anti-oxidative defense systems, immune cells show a more resistant character than cancer cells in the NIPP-induced apoptosis, which is an important reason why NIPP is considered promising in cancer management. Moreover, NIPP treatment induces immunogenic cell death of cancer cells, leading to maturation of dendritic cells and activation of cytotoxic CD8(+) T cells to further eliminate the cancer cells. Some studies also suggest that NIPP treatment may promote anti-tumor immune responses via other mechanisms such as inhibiting tumor angiogenesis and the desmoplasia of tumor stroma. Though more evidence is required, we expect a bright future for applying NIPP in clinical cancer management.