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Cytotoxic T Cells-mediated Immune Response01:27

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The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
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Cells undergoing apoptosis form apoptotic bodies that must be removed immediately to prevent inflammation, autoimmune diseases, and necrosis. Phagocytosis is carried out by professional phagocytes such as macrophages or  immature dendritic cells. Non-professional phagocytes such as  epithelial cells and fibroblasts also take part in this process; however, they are not as effective as professional phagocytes. 
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Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
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Immunogenic Apoptotic Cell Death and Anticancer Immunity.

Peter Vandenabeele1,2,3, Katrien Vandecasteele4, Claus Bachert5

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Advances in Experimental Medicine and Biology
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PubMed
Summary

Anticancer therapies can trigger immunogenic apoptosis, releasing damage-associated molecular patterns (DAMPs) that activate anti-tumor immunity. This review explores DAMP signaling, ER stress, and radiotherapy

Keywords:
ATPCalreticulinCancerChemotherapeuticsDAMPsER stressHMGB1RadiotherapyTumors

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Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death
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Area of Science:

  • Immunology
  • Cell Biology
  • Oncology

Background:

  • Apoptotic cells were traditionally considered anti-inflammatory.
  • Emerging evidence shows certain anticancer therapies induce immunogenic apoptosis.
  • This process involves damage-associated molecular patterns (DAMPs) activating anti-tumor immunity.

Purpose of the Study:

  • To review advances in danger signaling pathways and DAMP emission.
  • To discuss the role of ER stress in danger signaling.
  • To analyze radiotherapy-induced immunogenic apoptosis and its parameters.

Main Methods:

  • Review of experimental data and literature.
  • Discussion of danger signaling pathways (calreticulin, ATP, HMGB1).
  • Analysis of ER stress involvement and immunogenic cell death inducer classification.

Main Results:

  • Specific signaling pathways are activated by distinct immunogenic cell death stimuli.
  • ER stress plays a crucial role in danger signaling.
  • Radiotherapy-induced immunogenicity correlates with fraction dose and chemotherapy.

Conclusions:

  • Anticancer therapies can induce immunogenic apoptosis via DAMPs, activating anti-tumor immune responses.
  • ER stress is central to danger signaling and classifying cell death inducers.
  • Understanding radiotherapy parameters is key to optimizing its immunogenic potential.