Autophagy Modulates Immunogenic Cell Death in Cancer

Area of Science:

• Immunology
• Cell Biology
• Oncology

Background:

• Immunogenic cell death (ICD) triggers T-cell responses via damage-associated molecular patterns (DAMPs).
• Autophagy, a cellular degradation process, significantly influences antitumor immunity and the tumor microenvironment (TME).

Purpose of the Study:

• To summarize how autophagy impacts ICD-associated DAMPs.
• To explore autophagy's dual role in promoting or limiting ICD in various cancer models.
• To discuss the translational potential of modulating autophagy in cancer therapy.

Main Methods:

• Review of preclinical models examining autophagy's effect on ICD.
• Analysis of autophagy's impact on DAMPs, endoplasmic reticulum stress, and MHC presentation.
• Focus on hematological malignancies, including multiple myeloma.

Main Results:

• Autophagy can promote ICD by sustaining ER stress and secretory pathways.
• Autophagy can limit ICD by degrading DAMPs and MHC molecules, with outcomes dependent on context.
• The autophagy-related protein GABARAP is implicated in bortezomib-induced ICD in multiple myeloma.

Conclusions:

• The interplay between autophagy and ICD is complex and context-dependent.
• Modulating autophagy offers potential therapeutic strategies, particularly in combination with ICD-inducing agents.
• Further research is needed to safely harness the autophagy-ICD axis in clinical settings.