The concept of immunogenic cancer cell death (ICD), as originally observed during the treatment with several chemotherapeutics or ionizing irradiation, has revolutionized the view on the development of new anticancer therapies. ICD is defined by endoplasmic reticulum (ER) stress response, reactive oxygen species (ROS) generation, emission of danger-associated molecular patterns and induction of antitumor immunity. Here we describe known and emerging cancer cell death-inducing physical modalities, such as ionizing irradiation, ultraviolet C light, Photodynamic Therapy (PDT) with Hypericin, high hydrostatic pressure (HHP) and hyperthermia (HT), which have been shown to elicit effective antitumor immunity. We discuss the evidence of ICD induced by these modalities in cancer patients together with their applicability in immunotherapeutic protocols and anticancer vaccine development.
Keywords: ATP, Adenosine triphosphate; CRT, calreticulin; DAMPs, danger-associated molecular patterns; DC, dendritic cells; EGFR, endothelial growth factor receptor; ER, endoplasmic reticulum; HHP, high hydrostatic pressure, HMGB1, high-mobility group box 1; HSP, heat shock protein; HT, hyperthermia; Hyp-PDT, Hypericin-based Photodynamic therapy; ICD, immunogenic cell death; IFNγ, interferon-γ; NDV, Newcastle Disease Virus; ROS, reactive oxygen species; RT, radiotherapy; TLR, Toll-like receptor; UVC, ultraviolet C light; cancer immunotherapy; eIF2α, eukaryotic translation initiation factor 2α; high hydrostatic pressure; hyperthermia; immunogenic cell death; ionizing irradiation; photodynamic therapy with hypericin.