38
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Physical modalities inducing immunogenic tumor cell death for cancer immunotherapy

      review-article
      1 , 2 , * , 1 , 2 , 3 , 3 , 1 , 2 , *
      Oncoimmunology
      Taylor & Francis
      cancer immunotherapy, high hydrostatic pressure, hyperthermia, immunogenic cell death, ionizing irradiation, photodynamic therapy with hypericin, ATP, Adenosine triphosphate, CRT, calreticulin, DAMPs, danger-associated molecular patterns, DC, dendritic cells, EGFR, endothelial growth factor receptor, eIF2α, eukaryotic translation initiation factor 2α, ER, endoplasmic reticulum, HHP, high hydrostatic pressure, HMGB1, high-mobility group box 1, HT, hyperthermia, ICD, immunogenic cell death, HSP, heat shock protein, Hyp-PDT, Hypericin-based Photodynamic therapy, IFNγ, interferon-γ, NDV, Newcastle Disease Virus, ROS, reactive oxygen species, RT, radiotherapy, TLR, Toll-like receptor, UVC, ultraviolet C light

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          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.

          Related collections

          Most cited references96

          • Record: found
          • Abstract: found
          • Article: not found

          Combining radiotherapy and cancer immunotherapy: a paradigm shift.

          The therapeutic application of ionizing radiation has been largely based on its cytocidal power combined with the ability to selectively target tumors. Radiotherapy effects on survival of cancer patients are generally interpreted as the consequence of improved local control of the tumor, directly decreasing systemic spread. Experimental data from multiple cancer models have provided sufficient evidence to propose a paradigm shift, whereby some of the effects of ionizing radiation are recognized as contributing to systemic antitumor immunity. Recent examples of objective responses achieved by adding radiotherapy to immunotherapy in metastatic cancer patients support this view. Therefore, the traditional palliative role of radiotherapy in metastatic disease is evolving into that of a powerful adjuvant for immunotherapy. This combination strategy adds to the current anticancer arsenal and offers opportunities to harness the immune system to extend survival, even among metastatic and heavily pretreated cancer patients. We briefly summarize key evidence supporting the role of radiotherapy as an immune adjuvant. A critical appraisal of the current status of knowledge must include potential immunosuppressive effects of radiation that can hamper its capacity to convert the irradiated tumor into an in situ, individualized vaccine. Moreover, we discuss some of the current challenges to translate this knowledge to the clinic as more trials testing radiation with different immunotherapies are proposed.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            The cellular and molecular basis of hyperthermia.

            In oncology, the term 'hyperthermia' refers to the treatment of malignant diseases by administering heat in various ways. Hyperthermia is usually applied as an adjunct to an already established treatment modality (especially radiotherapy and chemotherapy), where tumor temperatures in the range of 40-43 degrees C are aspired. In several clinical phase-III trials, an improvement of both local control and survival rates have been demonstrated by adding local/regional hyperthermia to radiotherapy in patients with locally advanced or recurrent superficial and pelvic tumors. In addition, interstitial hyperthermia, hyperthermic chemoperfusion, and whole-body hyperthermia (WBH) are under clinical investigation, and some positive comparative trials have already been completed. In parallel to clinical research, several aspects of heat action have been examined in numerous pre-clinical studies since the 1970s. However, an unequivocal identification of the mechanisms leading to favorable clinical results of hyperthermia have not yet been identified for various reasons. This manuscript deals with discussions concerning the direct cytotoxic effect of heat, heat-induced alterations of the tumor microenvironment, synergism of heat in conjunction with radiation and drugs, as well as, the presumed cellular effects of hyperthermia including the expression of heat-shock proteins (HSP), induction and regulation of apoptosis, signal transduction, and modulation of drug resistance by hyperthermia.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              A novel pathway combining calreticulin exposure and ATP secretion in immunogenic cancer cell death.

              Surface-exposed calreticulin (ecto-CRT) and secreted ATP are crucial damage-associated molecular patterns (DAMPs) for immunogenic apoptosis. Inducers of immunogenic apoptosis rely on an endoplasmic reticulum (ER)-based (reactive oxygen species (ROS)-regulated) pathway for ecto-CRT induction, but the ATP secretion pathway is unknown. We found that after photodynamic therapy (PDT), which generates ROS-mediated ER stress, dying cancer cells undergo immunogenic apoptosis characterized by phenotypic maturation (CD80(high), CD83(high), CD86(high), MHC-II(high)) and functional stimulation (NO(high), IL-10(absent), IL-1β(high)) of dendritic cells as well as induction of a protective antitumour immune response. Intriguingly, early after PDT the cancer cells displayed ecto-CRT and secreted ATP before exhibiting biochemical signatures of apoptosis, through overlapping PERK-orchestrated pathways that require a functional secretory pathway and phosphoinositide 3-kinase (PI3K)-mediated plasma membrane/extracellular trafficking. Interestingly, eIF2α phosphorylation and caspase-8 signalling are dispensable for this ecto-CRT exposure. We also identified LRP1/CD91 as the surface docking site for ecto-CRT and found that depletion of PERK, PI3K p110α and LRP1 but not caspase-8 reduced the immunogenicity of the cancer cells. These results unravel a novel PERK-dependent subroutine for the early and simultaneous emission of two critical DAMPs following ROS-mediated ER stress.
                Bookmark

                Author and article information

                Journal
                Oncoimmunology
                Oncoimmunology
                KONI
                Oncoimmunology
                Taylor & Francis
                2162-4011
                2162-402X
                7 January 2015
                2014
                : 3
                : 12
                : e968434
                Affiliations
                [1 ]Sotio ; Prague, Czech Republic
                [2 ]Department of Immunology; 2nd Faculty of Medicine and University Hospital Motol; Charles University ; Prague, Czech Republic
                [3 ]Cell Death Research and Therapy (CDRT) Unit; Department of Molecular and Cell Biology; University of Leuven (KU Leuven) ; Leuven, Belgium
                Author notes
                [* ]Correspondence to: Irena Adkins; Email: adkins@ 123456sotio.com ; Radek Špíšek; Email: spisek@ 123456sotio.com
                Article
                968434
                10.4161/21624011.2014.968434
                4352954
                25964865
                9066bbd8-23fe-4ef2-8cca-ddb2597125b2
                © 2014 The Author(s). Published with license by Taylor & Francis Group, LLC© Irena Adkins, Jitka Fucikova, Abhishek D Garg, Patrizia Agostinis, and Radek Špíšek

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/3.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The moral rights of the named author(s) have been asserted.

                History
                : 31 July 2014
                : 17 September 2014
                : 19 September 2014
                Page count
                Figures: 2, Tables: 2, References: 127, Pages: 12
                Categories
                Review

                Immunology
                cancer immunotherapy,high hydrostatic pressure,hyperthermia,immunogenic cell death,ionizing irradiation,photodynamic therapy with hypericin,atp, adenosine triphosphate,crt, calreticulin,damps, danger-associated molecular patterns,dc, dendritic cells,egfr, endothelial growth factor receptor,eif2α, eukaryotic translation initiation factor 2α,er, endoplasmic reticulum,hhp, high hydrostatic pressure, hmgb1, high-mobility group box 1,ht, hyperthermia,icd, immunogenic cell death,hsp, heat shock protein,hyp-pdt, hypericin-based photodynamic therapy,ifnγ, interferon-γ,ndv, newcastle disease virus,ros, reactive oxygen species,rt, radiotherapy,tlr, toll-like receptor,uvc, ultraviolet c light

                Comments

                Comment on this article