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Author: Clemen, Ramona × Has files: Yes × Version: publishedVersion × Subject: immunity × WGL Institute: INP ×

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    Plasma, cancer, immunity
    (Bristol : IOP Publ., 2022) Bekeschus, Sander; Clemen, Ramona
    Albeit heavily investigated for several decades already, the importance of the immune system in targeting cancer has received wide clinical attention only in recent years. This is partly because of long-standing rather traditional concepts on tumor biology on the one hand and the complexity of the immune system and its processes on the other. The viewpoint of evaluating existing and emerging approaches in oncology based on toxicity to tumors and the ability to engage antitumor-immunity is gaining ground across several disciplines. Along those lines, cold physical plasma was suggested as potential anticancer tool more than a decade ago, but solid evidence of the immune system playing a role in plasma cancer treatment only emerged in recent years. Moreover, plasma may support cancer immunotherapies in the future. Cancer immunotherapies are systemic treatments with biologicals that were reported to synergize with existing local physical modalities before, such as radiotherapy and photodynamic therapy. This review outlines key concepts in oncology, immunology, and tumor therapy, links them to plasma research, and discusses immuno-oncological consequences. Finally, promising future clinical applications are summarized. Synoptically, first scientific evidence supports an immuno-oncological dimension of plasma cancer treatment in selected instances, but robust clinical evidence is still lacking. More basic and clinical research is needed to determine the immuno-molecular mechanisms and detailed plasma application modalities to facilitate real patient benefit in the long term.
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    Non-thermal plasma modulates cellular markers associated with immunogenicity in a model of latent HIV-1 infection
    (San Francisco, California, US : PLOS, 2021) Mohamed, Hager; Clemen, Ramona; Freund, Eric; Lackmann, Jan-Wilm; Wende, Kristian; Connors, Jennifer; Haddad, Elias K.; Dampier, Will; Wigdahl, Brian; Miller, Vandana; Bekeschus, Sander; Krebs, Fred C.; Kashanchi, Fatah
    Effective control of infection by human immunodeficiency virus type 1 (HIV-1), the causative agent of the acquired immunodeficiency syndrome (AIDS), requires continuous and life-long use of anti-retroviral therapy (ART) by people living with HIV-1 (PLWH). In the absence of ART, HIV-1 reemergence from latently infected cells is ineffectively suppressed due to suboptimal innate and cytotoxic T lymphocyte responses. However, ART-free control of HIV-1 infection may be possible if the inherent immunological deficiencies can be reversed or restored. Herein we present a novel approach for modulating the immune response to HIV-1 that involves the use of non-thermal plasma (NTP), which is an ionized gas containing various reactive oxygen and nitrogen species (RONS). J-Lat cells were used as a model of latent HIV-1 infection to assess the effects of NTP application on viral latency and the expression of pro-phagocytic and pro-chemotactic damage-associated molecular patterns (DAMPs). Exposure of J-Lat cells to NTP resulted in stimulation of HIV-1 gene expression, indicating a role in latency reversal, a necessary first step in inducing adaptive immune responses to viral antigens. This was accompanied by the release of pro-inflammatory cytokines and chemokines including interleukin-1β (IL-1β) and interferon-γ (IFN-γ); the display of pro-phagocytic markers calreticulin (CRT), heat shock proteins (HSP) 70 and 90; and a correlated increase in macrophage phagocytosis of NTP-exposed J-Lat cells. In addition, modulation of surface molecules that promote or inhibit antigen presentation was also observed, along with an altered array of displayed peptides on MHC I, further suggesting methods by which NTP may modify recognition and targeting of cells in latent HIV-1 infection. These studies represent early progress toward an effective NTP-based ex vivo immunotherapy to resolve the dysfunctions of the immune system that enable HIV-1 persistence in PLWH.