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

Cells. 2022 Apr 22;11(9):1415. doi: 10.3390/cells11091415.


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.

Keywords: DAMP; apoptosis; biomarker; bortezomib; decapeptide proTα(100–109); doxorubicin; immunogenic cell death; prothymosin alpha; regulated cell death; γ-radiation.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alarmins / metabolism
  • Biomarkers
  • Humans
  • Immunity
  • Immunogenic Cell Death*
  • Peptides
  • Protein Precursors
  • Thymosin* / analogs & derivatives
  • Thymosin* / pharmacology


  • Alarmins
  • Biomarkers
  • Peptides
  • Protein Precursors
  • prothymosin alpha
  • Thymosin