Cold Atmospheric Plasma Targeting Hematological Malignancies: Potentials and Problems of Clinical Translation

Abstract

Cold atmospheric plasma is an ionized gas produced near room temperature; it generates reactive oxygen species and nitrogen species and induces physical changes, including ultraviolet, radiation, thermal, and electromagnetic effects. Several studies showed that cold atmospheric plasma could effectively provoke death in a huge amount of cell types, including neoplastic cells, via the induction of apoptosis, necrosis, and autophagy. This technique seems able to destroy tumor cells by disturbing their more susceptible redox equilibrium with respect to normal cells, but it is also able to cause immunogenic cell death by enhancing the immune response, to decrease angiogenesis, and to provoke genetic and epigenetics mutations. Solutions activated by cold gas plasma represent a new modality for treatment of less easily reached tumors, or hematological malignancies. Our review reports on accepted knowledge of cold atmospheric plasma’s effect on hematological malignancies, such as acute and chronic myeloid leukemia and multiple myeloma. Although relevant progress was made toward understanding the underlying mechanisms concerning the efficacy of cold atmospheric plasma in hematological tumors, there is a need to determine both guidelines and safety limits that guarantee an absence of long-term side effects.

Cold Atmospheric Plasma Medicine: Applications, Challenges, and Opportunities for Predictive Control

“…The majority of these studies have been conducted using cell lines or in vitro treatment methods. Cell lines for hepatomas [91], leukemia [92], brain tumors [93], and several other cancers, including colorectal [94], breast [95], lung [96], cervical [97], and head and neck [97] cancer is all strongly affected by cold plasma treatments. The majority of these cancer cell lines constitutively produce low levels of hydrogen peroxide in the nanomolar range [25].…”

Current Status and Future Trends of Cold Atmospheric Plasma as an Oncotherapy

“…In adaptive immunity, CAP acted as a unique RONS delivery system to stimulate the immune system and promote an anticancer immune response ( Bekeschus et al ., 2017 ; Lin et al ., 2019 ; Duchesne et al ., 2021 ; Gangemi et al ., 2022 ; Min et al ., 2022 ). CAP reversed the downregulated immune response in glioblastoma multiforme ( Almeida et al ., 2019 ) and promoted the tumour recruitment of immune cells by releasing immune stimulation signals in the TME of pancreatic cancer cells ( Lin et al ., 2018 ; Almeida et al ., 2019 ; Van Loenhout et al ., 2019 ).…”

“…The anticancer potential of CAP was first reported in 2007 when treating melanoma (Yan et al, 2017c;Zhou et al, 2020). Since then, there have been consecutive reports of success using CAP to selectively induce programmed death events such as apoptosis (Xiang et al, 2018), necrosis (Hoffmann et al, 2013), autophagy (Liu et al, 2022) and immunogenic cell death (ICD) (Van Loenhout et al, 2019); to halt tumour cell migration (Wang et al, 2021); to rewire malignant cell metabolism; and to arrest cancer stemness (Dai et al, 2022), the processes of which involve both genetic and epigenetic alterations (Dai et al, 2020a;Gangemi et al, 2022). The anticancer efficacy of CAP has been demonstrated in approximately 30 tumours, including breast cancer (Xiang et al, 2018;, glioma (Yang et al, 2021), pancreatic cancer (Van Loenhout et al, 2019), bladder cancer (Wang et al, 2021), prostate cancer (Hua et al, 2021), and liver cancer (Liu et al, 2022).…”

Cold Air Plasma Inhibiting Tumor-Like Biological Behavior of Rheumatoid Arthritis Fibroblast-Like Synovial Cells via G2/M Cell Cycle Arrest

“…Cold air plasma (CAP) is an ionized neutral gas that is primarily made up of reactive oxygen species (ROS), reactive nitrogen species (RNS), electrons, ions, and ultraviolet photons. 11 CAP is used in the medical field because it is close to room temperature. CAP has demonstrated clear anticancer potential in vitro and in vivo in a large number of studies over the last ten years.…”