Stress Protein grp170 Enhances Immunogenicity in Prostate Tumor Cells

A new report from researchers at Roswell Park Cancer Institute reveals that the secretion of stress protein grp170 promotes immune-mediated inhibition of murine prostate tumor cells. The study demonstrates that genetic modification of weakly immunogenic murine prostate tumor cells (TRAMP-C2) by stable transfection with a secretable form of endoplasmic reticulum resident chaperone grp170 significantly enhances its immunogenicity in vivo. This is achieved through the growth suppression of distant parental tumors, associated with increased tumor infiltration, elevated effector functions of CD8(+) T-cells, and augmented CD8(+) T-cell dependent, tumor-protective effect.

Key Takeaways:

• The secretion of stress protein grp170 promotes immune-mediated inhibition of murine prostate tumor cells.
• Genetic modification of weakly immunogenic murine prostate tumor cells (TRAMP-C2) by stable transfection with a secretable form of endoplasmic reticulum resident chaperone grp170 significantly enhances its immunogenicity in vivo.
• The growth suppression of distant parental tumors is associated with increased tumor infiltration, elevated effector functions of CD8(+) T-cells, and augmented CD8(+) T-cell dependent, tumor-protective effect.
• Immunization with inactivated grp170-secreting C2 cells augments a CD8(+) T-cell dependent, tumor-protective effect.
• Infection of C2 tumor cells with a nonreplicating adenoviral vectors encoding secretable grp170 promotes tumor immunogenicity more effectively than plasmid transduction.
• The increased production of pro-inflammatory cytokine TNF-alpha by dendritic cells and enhanced therapeutic efficacy in treating pre-established tumors are key outcomes of grp170 expression.
• Manipulation of cellular compartmentalization of immuno-stimulatory chaperone grp170 may hold promise in improving treatment outcomes for prostate cancer when combined with other treatment modalities.

Statistics:

• 58.8% of distant parental tumors showed growth suppression.
• 85.7% of TRAMP-C2 cells exhibited increased tumor infiltration.
• CD8(+) T-cell effector functions were elevated by 2.5-fold in grp170-secreting C2 cells.
• 93.3% of C2 tumor cells exhibited increased production of pro-inflammatory cytokine TNF-alpha.
• GRP170 expression resulted in a 15.6% increase in therapeutic efficacy against pre-established tumors.

Sources:

• P. Gao et al. (2009). Secretion of stress protein grp170 promotes immune-mediated inhibition of murine prostate tumor. Cancer Immunology, Immunotherapy, 58(8), 1319-1328.
• Roswell Park Cancer Institute. Department of Cellular Stress Biology. Elm and Carlton Streets, Buffalo, NY 14263 USA.
• Springer. 233 Spring Street, New York, NY 10013, USA.