120 - ROS-targeting of melanoma cells provides immuno-protection against tumor growth

Abstract

Breaking barriers in science necessitates crossing of boundaries between disciplines. An intimate link is presented that connects the fields of redox research, cancer therapy, and immunology. Immunogenic cancer cell death (ICD) provides inflammatory stimuli to elicit anti-tumor adaptive immune responses. Release of adjuvant find-me (HMGB1, ATP) and eat-me (calreticulin) signals facilitates DC maturation and cross presentation of neoantigens to T cells. Key hallmarks of ICD in tumor cells are stress of the endoplasmic reticulum and the unfolded proteins response. Both are known to be subject to redox control. Potent ICD-inducing therapies are drugs such as anthracyclines, ionizing irradiation, or photodynamic therapies. Intriguingly, these antitumor approaches are reported to show concomitant generation of reactive species that can drive signaling responses through redox relays. Hence, the importance of reactive species and specifically hydrogen peroxide signaling are underappreciated in the onset of ICD in cancer cells. Recently, a novel technology capable of generating various oxidants has not only been shown to confer remarkable effects in tumor-bearing mice but is also a potent ICD inducer. This cold physical plasma, a partially ionized gas at about body temperature, can be applied to tumors topically, and first palliative cancer patients benefited from plasma therapy. Experimental evidence will be presented that i) physical plasma is an ICD inducer in various cell types including melanoma, ii) this is concomitant with a global HMOX1 signature, and iii) plasma-derived ROS evoke an antitumor T-cell response in tumor-bearing mice.