Immunogenic Cell Death, DAMPs and Prothymosin α as a Putative Anticancer Immune Response Biomarker

Cells - Tập 11 Số 9 - Trang 1415
Anastasios I. Birmpilis1, A. Paschalis2,3,1, Apostolis Mourkakis4, Panayiota Christodoulou4, Ioannis V. Kostopoulos1, Elina Antimissari4, Georgia I. Terzoudi5, Alexandros G. Georgakilas2, Christina Armpilia3, Panagiotis Papageorgis6, Efstathios Kastritis7, Evangelos Terpos7, Meletios Α. Dimopoulos7, Hubert Kalbacher8,9, Evangelia Livaniou10, Maria Christodoulou4, Ourania E. Tsitsilonis1,4
1Section of Animal and Human Physiology, Department of Biology, School of Sciences, National and Kapodistrian University of Athens, Panepistimiopolis, Ilissia, 15784 Athens, Greece.
2DNA Damage Laboratory, Physics Department, School of Mathematical and Physical Sciences, National Technical University of Athens, 15780 Zografou, Greece.
3Medical Physics Unit, 1st Department of Radiology, School of Medicine, Aretaieion Hospital, National and Kapodistrian University of Athens, 11528 Athens, Greece.
4Tumor Immunology and Biomarkers Laboratory, Basic and Translational Cancer Research Center, Department of Life Sciences, European University Cyprus, Nicosia 2404, Cyprus.
5Laboratory of Health Physics, Radiobiology & Cytogenetics, Institute of Nuclear and Radiological Sciences and Technology, Energy and Safety, National Centre for Scientific Research "Demokritos", Agia Paraskevi, 15310 Athens, Greece.
6Tumor Microenvironment, Metastasis and Experimental Therapeutics Laboratory, Basic and Translational Cancer Research Center, Department of Life Sciences, European University Cyprus, Nicosia 2404, Cyprus.
7Department of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens, 11528, Athens, Greece
8Institute of Clinical Anatomy and Cell Analysis, Eberhard Karls Universität Tübingen, 72074 Tübingen, Germany.
9Interfaculty Institute of Biochemistry, Eberhard Karls Universität Tübingen, 72076 Tübingen, Germany.
10Immunopeptide Chemistry Laboratory, Institute of Nuclear and Radiological Sciences and Technology, Energy and Safety, National Centre for Scientific Research "Demokritos", Agia Paraskevi, 15310 Athens, Greece.

Tóm tắt

The new and increasingly studied concept of immunogenic cell death (ICD) revealed a previously unknown perspective of the various regulated cell death (RCD) modalities, elucidating their immunogenic properties and rendering obsolete the notion that immune stimulation is solely the outcome of necrosis. A distinct characteristic of ICD is the release of danger-associated molecular patterns (DAMPs) by dying and/or dead cells. Thus, several members of the DAMP family, such as the well-characterized heat shock proteins (HSPs) HSP70 and HSP90, the high-mobility group box 1 protein and calreticulin, and the thymic polypeptide prothymosin α (proTα) and its immunoreactive fragment proTα(100–109), are being studied as potential diagnostic tools and/or possible therapeutic agents. Here, we present the basic aspects and mechanisms of both ICD and other immunogenic RCD forms; denote the role of DAMPs in ICD; and further exploit the relevance of human proTα and proTα(100–109) in ICD, highlighting their possible clinical applications. Furthermore, we present the preliminary results of our in vitro studies, which show a direct correlation between the concentration of proTα/proTα(100–109) and the levels of cancer cell apoptosis, induced by anticancer agents and γ-radiation.

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