Clinically relevant GABARAP deficiency abrogates bortezomib-induced immunogenic cell death in multiple myeloma

Oncoimmunology. 2024 May 27;13(1):2360275. doi: 10.1080/2162402X.2024.2360275. eCollection 2024.

Abstract

Recently, it was revealed that the high-risk, poor-prognosis downregulation of GABA type A receptor-associated protein (GABARAP) causes a defect in both autophagy and surface exposure of calreticulin (CALR) in multiple myeloma (MM) cells responding to bortezomib. Hence, GABARAP-defective MM cells fail to undergo immunogenic cell death.

Keywords: Immunotherapy; autophagy; danger associated molecular pattern; phagocytosis.

MeSH terms

  • Adaptor Proteins, Signal Transducing* / deficiency
  • Adaptor Proteins, Signal Transducing* / genetics
  • Adaptor Proteins, Signal Transducing* / metabolism
  • Antineoplastic Agents* / pharmacology
  • Antineoplastic Agents* / therapeutic use
  • Apoptosis Regulatory Proteins* / genetics
  • Apoptosis Regulatory Proteins* / metabolism
  • Autophagy / drug effects
  • Bortezomib* / pharmacology
  • Bortezomib* / therapeutic use
  • Calreticulin / genetics
  • Calreticulin / metabolism
  • Cell Line, Tumor
  • Humans
  • Immunogenic Cell Death* / drug effects
  • Microtubule-Associated Proteins* / genetics
  • Microtubule-Associated Proteins* / metabolism
  • Multiple Myeloma* / drug therapy
  • Multiple Myeloma* / genetics
  • Multiple Myeloma* / immunology
  • Multiple Myeloma* / metabolism
  • Multiple Myeloma* / pathology

Substances

  • Bortezomib
  • Adaptor Proteins, Signal Transducing
  • Antineoplastic Agents
  • Microtubule-Associated Proteins
  • Apoptosis Regulatory Proteins
  • GABARAP protein, human
  • Calreticulin