Abstract 3710: Components of HLA class I molecules influence pancreatic cancer cell proliferation and migration

Human leukocyte antigen (HLA) class I molecules are composed of a heavy chain with three isoforms (-A, -B, and –C) and a light chain (beta 2-microglobulin or β2m). These molecules are best known for their role within the immune system, in which they present antigens to cytotoxic T cells. These molecules have been found in some tumor models to be down regulated as a form of immune escape; however, recent studies in breast, gastric, and lung cancer have correlated high expression levels of HLA class I with a poorer patient prognosis. β2m has also been found to be high in expression in many cancers, and it has been implicated in promoting renal cancer progression by increasing proliferation and migration. Whether any components of the HLA class I molecule contribute to the pathogenesis of other cancers, such as pancreatic cancer, has not been elucidated. Our recent results show that human pancreatic cancer cell lines have high total and cell-surface expression of β2m, HLA-A, and HLA-B, with the exception of one pancreatic cancer cell line that we found exhibits low expression of HLA-B. Furthermore, differential gene expression analysis performed on laser capture-microdissected human pancreatic cancer patient samples revealed that HLA-B expression is not reduced in pancreatic ductal adenocarcinoma cells, compared to precursor (PanIN) epithelial or stromal cells. Together, our results indicate that pancreatic cancer cells have not selectively down regulated HLA class I molecule expression. This observation suggests that HLA class I molecules might provide some benefit to pancreatic cancer cells that counterbalances any risk of immune attack caused by HLA class I molecules. To examine whether the components of the HLA class I molecule actually confer potential advantages to pancreatic cancer cells, we transfected siRNA specific for β2m, HLA-A heavy chain, or HLA-B heavy chain into several pancreatic cancer cell lines and evaluated the effects on their proliferation and migration. Down-regulation of either β2m or HLA-B expression slowed the proliferation of one pancreatic cancer cell line, whereas down-regulation of HLA-A expression had the inverse effect on the same cell line. Two other pancreatic cancer cell lines had an opposite phenotype: proliferating more slowly when HLA-A expression was reduced, but more rapidly when HLA-B expression was decreased. Our investigation of the impact of down regulating HLA class I molecule components on the migration of pancreatic cancer cells showed the same trends with each cell line as we had observed in our proliferation analyses. In conclusion, we found that pancreatic cancer cells express substantial levels of HLA class I molecule components, and that these components significantly influence the proliferation and migration of pancreatic cancer cell lines in a manner that varies for HLA-A versus HLA-B, and that also varies in pattern among the types of pancreatic cancer cell lines. Citation Format: Bailee Sliker, Cassie Liu, Brittany Poelaert, H Carlo Maurer, Kenneth P. Olive, Joyce C. Solheim. Components of HLA class I molecules influence pancreatic cancer cell proliferation and migration [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3710. doi:10.1158/1538-7445.AM2017-3710