## 1 Introduction  
In cancer, the infiltration of pro-inflammatory immune cells can be a major prognostic factor in patient survival [1; 2]. Among others, macrophages are given an outstanding role in this process. Macrophages stem from monocytes, which stream into the target tissue from the blood by diapedesis prior to differentiation [3]. Their main role is the regulation of inflammation [4]. For example, they recognize and clear pathogens, phagocytose apoptotic and necrotic cells, and attract or repel other leucocyte populations or stromal cells by releasing a number of cytokines and chemokines. By doing so, macrophages play a central role in tissue hemostasis and disease, for example, in non-healing wounds and cancer [5]. This includes the development [6] as well as the progression of cancer [7] as circulatingmonocytes frequently enter the tumor bed [8]. However, education of macrophages through the tumor can enhance tumor-growth and complications, as metastasis [9; 10]. For example, it has been reported that colorectal cancer can polarize monocytes to macrophages via tumor-microvesicles [11]. On the other hand, driving the differentiation of monocytes to a more pro-immunogenic phenotype can reverse the effect and reveal an anti-cancer activity [7; 12; 13]. This makes tumor associated macrophages a promising target for immune therapies [14; 15] as hot (inflamed) tumors are often associated with a better prognosis [16; 17].  
A body of evidence points to an important role of reactive oxygen and nitrogen species in these processes [18]. In tissues, monocytes and macrophages are often exposed to reactive oxygen and/or nitrogen species (ROS/RNS) released under inflammatory conditions mainly from other myeloid cells [19]. Moreover, the activation of macrophages and the subsequent oxidative environment has been a topic in recent research [20; 21]. Together with local cytokines and chemokines provided by the inflamed microenvironment, phenotypic differentiation takes place [22]. In general, ROS/RNS readily react with membranes and protein-thiols redox-signaling oxidative changes to unleash appropriate transcriptional responses [23; 24; 25]. It has been hypothesized that this signaling system can be exploited by technical generation of ROS/RNS.  
Therapeutic ROS/RNS are generated with cold physical plasma devices. Cold physical plasma, from hereon named plasma, is a partially ionized gas at body temperature [26]. This multi-component system is releasing a variety of ROS/RNS, such as, nitric oxide, superoxide, and singlet oxygen [27; 28; 29]. At present, three medical plasmas have received accreditation as medical devices [30]. Plasmas are antimicrobial and suggested to support healing of chronic-wounds and ulcers in pre-clinical and clinical studies [31; 32; 33; 34; 35; 36]. Furthermore, cold plasmas have successfully eradicated tumors in mice [37; 38; 39; 40; 41], and first cancer patients have benefited from plasma therapy [42]. Hence, plasma treatment is performed in wounds and topical cancer, both being active sites of monocyte influx. To investigate how plasma treatment may affect these cells regarding activity, differentiation, and function, human monocytes (either naive or pre-stimulated as would be the case when approaching inflammatory sites) were plasma-treated in vitro and investigated regarding their activity and phenotype. Our results suggested that ROS/RNS derived from plasma shape a differentiation profile in human monocytes.