Is the inter-patient coincidence of a subclinical disorder related to EHR similarity?

10.1109/HEALTH.2011.60267382011 IEEE 13th International Conference on e-Health Networking, Applications and Services, HEALTHCOM 2011177-18

A SNOMED supported ontological vector model for subclinical disorder detection using EHR similarity

10.1016/j.engappai.2011.05.013Engineering Applications of Artificial Intelligence2481398-1409EAAI

Progranulin mediates immune evasion of pancreatic ductal adenocarcinoma through regulation of MHCI expression

Immune evasion is indispensable for cancer initiation and progression, although its underlying mechanisms in pancreatic ductal adenocarcinoma (PDAC) are not fully known. Here, we characterize the function of tumor-derived PGRN in promoting immune evasion in primary PDAC. Tumor- but not macrophage-derived PGRN is associated with poor overall survival in PDAC. Multiplex immunohistochemistry shows low MHC class I (MHCI) expression and lack of CD8(+) T cell infiltration in PGRN-high tumors. Inhibition of PGRN abrogates autophagy-dependent MHCI degradation and restores MHCI expression on PDAC cells. Antibody-based blockade of PGRN in a PDAC mouse model remarkably decelerates tumor initiation and progression. Notably, tumors expressing LCMV-gp33 as a model antigen are sensitized to gp33-TCR transgenic T cell-mediated cytotoxicity upon PGRN blockade. Overall, our study shows a crucial function of tumor-derived PGRN in regulating immunogenicity of primary PDAC