High hydrostatic pressure affects antigenic pool in tumor cells: Implication for dendritic cell-based cancer...

Area of Science:

• Oncology
• Immunology
• Biotechnology

Background:

• Dendritic cell (DC)-based active immunotherapy shows promise for various cancers.
• High hydrostatic pressure (HHP) is a method explored for generating cancer immunotherapies.

Purpose of the Study:

• To investigate the impact of HHP on tumor antigen degradation and immunogenicity in different cancer cell lines.
• To optimize HHP treatment parameters for generating effective cancer cells for DC-based immunotherapy, particularly for lung cancer.

Main Methods:

• Treatment of human prostate, lung, and ovarian cancer cell lines with varying HHP levels (up to 300MPa).
• Analysis of tumor antigen and mRNA degradation post-HHP treatment.
• Comparison of immunogenicity and DC phagocytosis of HHP-treated lung cancer cells (150, 200, 250MPa).

Main Results:

• HHP treatment caused antigen degradation, with lung cancer cells showing significant antigen loss at 250MPa.
• Tumor antigen-coding mRNA was rapidly reduced at 200MPa across all tested cell lines.
• HHP at 150MPa induced immunogenic cell death but impaired DC phagocytosis; 200MPa provided an optimal balance for immunogenic killing and antigen delivery to DCs.

Conclusions:

• HHP treatment parameters must be carefully selected based on cancer cell line sensitivity and desired therapeutic outcome.
• 200MPa HHP treatment of lung cancer cells is optimal for generating immunogenic killed cells for DC-based immunotherapy.
• These findings provide crucial preclinical data for an ongoing NSCLC clinical trial using DCVAC/LuCa.