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Immunogenic cell stress and death.

Guido Kroemer1,2,3, Claudia Galassi4, Laurence Zitvogel5,6,7,8,9

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Cell death signals influence immune responses. Immunogenic cell death (ICD) is crucial for immunosurveillance, and its dysregulation may contribute to autoimmune disorders.

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Area of Science:

  • Immunology
  • Cell Biology
  • Oncology

Background:

  • Dying mammalian cells release signals that modulate host immune responses.
  • Cell death can trigger inflammation or adaptive immunity depending on cellular antigenicity.

Purpose of the Study:

  • To explore the role of immunogenic cell death (ICD) in immunosurveillance and its implications in various diseases.
  • To investigate how pathogens and cancer cells evade immune detection of cell death.
  • To examine the potential involvement of ICD in non-infectious, non-malignant autoimmune disorders.

Main Methods:

  • Analysis of cellular signaling pathways during cell death.
  • Investigation of antigen presentation by dying cells.
  • Evaluation of immune responses to dying cells in different pathological contexts.

Main Results:

  • Cell death signals dictate whether inflammation or adaptive immunity is engaged.
  • Antigenic cell death, particularly in infected or malignant cells, can initiate cytotoxic T lymphocyte responses and immunological memory.
  • Pathogens and cancer cells have evolved mechanisms to evade immune recognition of their death.
  • Normal cells undergoing stress can generate neoantigens, potentially driving antigen-specific immunity and contributing to autoimmunity.

Conclusions:

  • Immunogenic cell death (ICD) plays a critical role in immunosurveillance against pathogens and cancer.
  • Mechanisms exist to suppress ICD recognition, highlighting evolutionary adaptations.
  • ICD may be implicated in the development of autoimmune diseases linked to autoreactivity.