Improving Tumor Immunotherapy

SLU ID 19-010 | Reprogramming lipid metabolism

Background

The development of T cell senescence driven by both malignant tumor cells and regulatory T cells (Treg) is a general feature in cancers. Senescent T cells have active glucose metabolism but exhibit unbalanced lipid metabolism, resulting in changes of expression of lipid metabolic enzymes and lipid species and accumulation of lipid droplets (LDs). Elevated group IVA phospholipase A₂ (cPLA2α) is responsible for the altered lipid metabolism and senescence induction in T cells mediated by Treg and tumor cells, which involves MAPK and STAT signaling.

Overview

Researchers at Saint Louis University have demonstrated that development of T cell senescence driven by both malignant tumor cells and regulatory T (Treg) cells is a general feature in cancers. They have identified new mechanistic links between T cell senescence and regulation of lipid metabolism in the tumor microenvironment as well as a new target (cPLA2α) to reprogram T cell lipid metabolism for tumor immunotherapy.

Benefits

The potential benefits of this technology include:

• Increasing the efficacy of cancer therapies

• Minimizing the efficacy variability among tumor types

• Increasing understanding of the mechanisms responsible for T-cell dysfunctional states

• Increasing the number of potential therapeutics to treat cancers

Applications

Potential applications of this technology include:

• tumor immunotherapies development

Opportunity

Saint Louis University is seeking partners to further develop and commercialize this technology.

References

• Yang, W. et al. Potentiating the antitumour response of CD8(+) T cells by modulating cholesterol metabolism. Nature 531, 651-655, doi:10.1038/nature17412 (2016).