title: Circulating nucleosomes and biomarkers of immunogenic cell death as predictive and prognostic markers in cancer patients undergoing cytotoxic therapy.
abstract: BACKGROUND
  Immunogenic cell death markers are released from apoptotic and necrotic cells upon pathologic or therapeutic causes and stimulate the innate and adaptive immune system. Cell death products such as nucleosomes, damage-associated molecular pattern (DAMP) molecules such as the high-mobility group box 1 protein (HMGB1) and its receptor of advanced glycation end products (sRAGE) are supposed to play an essential role in driving this process. However, this immunogenic activation may have dual effects, either by sensitizing the immune system for more efficient tumor cell removal or by creating a favorable tumor microenvironment that facilitates tumor growth, proliferation and invasiveness.
  
  
  METHODS
  Here, we review recent findings on the relevance of serum nucleosomes, DNAse activity, HMGB1 and sRAGE as biomarkers for the diagnosis, prognosis and therapy prediction in cancer disease.
  
  
  CONCLUSIONS
  In comparison with healthy controls, cancer patients demonstrated elevated serum levels of nucleosomes and HMGB1 while sRAGE levels were decreased. During locoregional and systemic cytotoxic therapies, a high release of nucleosomes and HMGB1 as well as low release of sRAGE before and during the initial phase of the treatment was found to be associated with poor response to the therapy and patient survival. Therefore, immunogenic cell death markers are promising tools for the prognosis, therapy prediction and monitoring in cancer patients.
authors.affiliation: Haematology/Oncology Outpatient Specialty Center, Franz-Schrank-Str. 2, 80638 Munich, Germany.
authors.forename: Oliver J
authors.initials: OJ
authors.lastname: Stoetzer
authors.forename: Christin
authors.initials: C
authors.lastname: Wittwer
authors.forename: Julia
authors.initials: J
authors.lastname: Lehner
authors.forename: Yvonne N
authors.initials: YN
authors.lastname: Fahmueller
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Kohles
authors.forename: Debora M I
authors.initials: DM
authors.lastname: Fersching
authors.forename: Gloria
authors.initials: G
authors.lastname: Leszinski
authors.forename: Juliane
authors.initials: J
authors.lastname: Roessner
authors.forename: Stefan
authors.initials: S
authors.lastname: Holdenrieder
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D016923:Cell Death; D006801:Humans; D009369:Neoplasms / Q000097:blood* / Q000188:drug therapy / Q000473:pathology; D009707:Nucleosomes / Q000378:metabolism*; D011379:Prognosis
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D009707:Nucleosomes