Immunomodulatory Effect of Proteasome Inhibitors via the Induction of Immunogenic Cell Death in Myeloma Cells.
Maiko MatsushitaSho KashiwazakiSatoshi KamikoMichio KoboriMakoto OsadaHisako KuniedaMaki HiraoDaiju IchikawaYutaka HattoriPublished in: Pharmaceuticals (Basel, Switzerland) (2023)
Several anti-cancer drugs are known to have immunomodulatory effects, including immunogenic cell death (ICD) of cancer cells. ICD is a form of apoptosis which is caused by the release of damage-associated molecular patterns (DAMPs), the uptake of cancer antigens by dendritic cells, and the activation of acquired immunity against cancer cells. ICD was originally reported in solid tumors, and there have been few reports on ICD in multiple myeloma (MM). Here, we showed that proteasome inhibitors, including carfilzomib, induce ICD in myeloma cells via an unfolded protein response pathway distinct from that in solid tumors. Additionally, we demonstrated the potential impact of ICD on the survival of patients with myeloma. ICD induced by proteasome inhibitors is expected to improve the prognosis of MM patients not only by its cytotoxic effects, but also by building strong immune memory response against MM cells in combination with other therapies, such as chimeric antigen receptor-T cell therapy.
Keyphrases
- cell cycle arrest
- cell death
- multiple myeloma
- induced apoptosis
- dendritic cells
- cell therapy
- endoplasmic reticulum stress
- newly diagnosed
- pi k akt
- oxidative stress
- end stage renal disease
- signaling pathway
- immune response
- ejection fraction
- emergency department
- chronic kidney disease
- stem cells
- squamous cell carcinoma
- working memory
- mesenchymal stem cells
- binding protein
- young adults
- risk assessment
- patient reported outcomes
- human health
- amino acid
- adverse drug