title: Until Death Do Us Part: Necrosis and Oxidation Promote the Tumor Microenvironment.
abstract: Tumor proliferation is concomitant with autophagy, limited apoptosis, and resultant necrosis. Necrosis is associated with the release of damage-associated molecular pattern molecules (DAMPs), which act as 'danger signals', recruiting inflammatory cells, inducing immune responses, and promoting wound healing. Most of the current treatment strategies for cancer (chemotherapy, radiation therapy, hormonal therapy) promote DAMP release following therapy-induced tumor death by necroptosis and necrosis. Myeloid cells (monocytes, dendritic cells (DCs), and granulocytes), as well as mesenchymal stromal cells (MSCs) belong to the early immigrants in response to unscheduled cell death, initiating and modulating the subsequent inflammatory response. Responding to DAMPs, MSCs, and DCs promote an immunosuppressive milieu, while eosinophils induce oxidative conditions limiting the biologic activity of DAMPs over time and distance. Regulatory T cells are strongly affected by pattern recognition receptor signaling in the tumor microenvironment and limit immune reactivity coordinately with myeloid-derived suppressor cells. Means to 'aerobically' oxidize DAMPs provide a novel strategy for limiting tumor progression. The present article summarizes our current understanding of the impact of necrosis on the tumor microenvironment and the influence of oxidative conditions found within this setting.
authors.affiliation: Institute for Transfusion Medicine, University Hospital Ulm, Ulm, Germany; Institute for Clinical Transfusion Medicine and Immunogenetics Ulm, German Red Cross Blood Services Baden-Württemberg-Hessen, Ulm, Germany.
authors.forename: Ramin
authors.initials: R
authors.lastname: Lotfi
authors.affiliation: University of Pittsburgh Schools of the Health Sciences G.27A Hillman Cancer Center, Pittsburgh, PA, USA.
authors.forename: Christof
authors.initials: C
authors.lastname: Kaltenmeier
authors.affiliation: University of Pittsburgh Schools of the Health Sciences G.27A Hillman Cancer Center, Pittsburgh, PA, USA.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Lotze
authors.affiliation: Department of Otorhinolaryngology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Bergmann