Epstein-Barr virus latent membrane protein 2A mediated activation of Sonic Hedgehog pathway induces HLA class Ia downregulation in gastric cancer cells

- EBV LMP2A activates the Sonic Hedgehog pathway in Gastric Cancer cells.
- EBV LMP2A decreases HLA ABC expression in gastric cancer cells.
- LMP2A utilizes the Sonic Hedgehog pathway to decrease HLA ABC expression.
- This decrease in HLA Class Ia expression is Gli1 dependent.

One of the immune evasion strategies manifested by malignant cells is the downregulation of the Human Leukocyte Antigen (HLA). HLA Class I (HLA- A, -B, -C) present endogenous peptides including viral and tumor antigens to cytotoxic T lymphocytes for immune mediated destruction. We have found the Epstein Barr Virus (EBV) Latent Membrane Protein 2A (LMP2A) to be responsible for this HLA downregulation in gastric cancer cells. Our results further indicate the Sonic Hedgehog pathway; primarily Gli1 to bring about the LMP2A mediated decrease in HLA expression.