The effect of pseudohypoxia on the immune microenvironment of pancreatic neuroendocrine neoplasms (PanNEN)

#3796

Introduction: Pancreatic neuroendocrine tumors may develop sporadically or as part of an inherited disease, such as von Hippel-Lindau (VHL). VHL disease is caused by a germline pathogenic variant in the VHL gene encoding VHL protein (pVHL). Hypoxia inducible factor (HIF) is responsible for cellular oxygen supply. Its degradation is mediated in normoxic states via ubiquitination and inhibited by pVHL. Hence, pVHL deficiency leads to pseudohypoxia due to HIF overexpression. Several studies suggested immunomodulatory role for HIF in kidney cancer.

Aim(s): To assess the impact of pseudohypoxia on PanNET immune tumor microenvironment (iTME).

Materials and methods: Whole genome DNA methylation data of 16 vPanNET and 23 sPanNET, processed by Illumine Infinium EPIC Array and analysed using ChAMP on RStudio. Immune cells compositions were compared using methylation-based deconvolution algorithms (MethylResolver, Robust Partial Correlations, Constrained Projection and Cibersort) and gene set enrichment analysis identified pathways affected in each group based on promoter methylation analysis.

Conference:

Presenting Author:

Authors: Solomon Chmelnik A, Telerman A, Tirosh A,

Keywords: Pancreatic neuroendocrine tumor, VHL, DNA methylation, Immune cells, PD-L1,