MAY 19, 2020 1:15 PM EDT | APAC MAY 20, 2020 4:15 PM CST

Immune Infiltration Influences the Survival of Pancreatic Cancer Patients

Speaker
  • Assistant Professor, Group Leader of the Tumor Immuno-Pathology (TIP) Laboratory, Erasmus University Medical Center
    Biography
      Dana Adel Mustafa is a biologist and a cancer researcher at Erasmus medical Center, Rotterdam, The Netherlands. She mainly studies two of the most deadly cancers: pancreatic cancer and brain tumors. Her research aims to reveal the immune regulation and infiltration in various types of cancers. In addition, her group focuses in identifying circulating biomarkers for detecting the response to therapy. She is interested in cancer metabolism, and in connecting the metabolic and genomics maps. She has been using various -omics technologies to identify the new prevention targets. Following by the state-of-the-art organ-on-a chip and organoid models to validate the usefulness of the new discoveries. Working with and for people like patients and students is dr. Mustafa's drive. Therefore, she became an assistant professor and a group leader of the Tumor Immuno-Pathology (TIP) lab in 2017. She became a member of a big consortium of Oncolytic Viro-Immune therapy (OVIT) to create new therapeutic options for cancer patients. Dr. Mustafa strongly believe that we can make progress in the battle against this disease by extensive collaboration between various people, disciplines and institutions.

    Abstract

    Rational: Pancreatic Ductal Adenocarcinoma (PDAC) is a highly aggressive disease associated with poor outcome. Most PDAC patients die within the first two years, and only a small subgroup of patients exceeds this survival rate. So far, factors and pathways underlying long-term survivorship in PDAC are unknown. In a previous study we showed that high CD8/FoxP3 ratio is associated with a favorable outcome. Therefore, we aimed to reveal the immune-related key players that drive the long-term survivorship in PDAC patients.

    Methods: The immune-related gene expression profiles of 10 PDAC patients survived and free of recurrence for ≥ 5 years, was compared to 10 PDAC patients in whom recurrence and death occurred within 6 months after surgery. Samples were profiled using the PanCancer Immune Profiling Panel of nanoString technology. Subsequently, a subgroup of samples was measured by the GeoMx Digital Spatial Profiler (DSP) to determine the spatial location of the immune cells.

    Results: The immune microenvironment in long-term survivors was altered differentially than that of the short-term survivors. B cells were found to be highly expressed in long-term survivors by gene expression profile. The presence of B cells was confirmed by performing a high-plex proteomic analysis with spatial resolution (GeoMx DSP). B cells infiltrated to the tumor stroma together with T cells and antigen presenting cells in long-term survivors.

    Conclusion: This is the first comprehensive study that compares the expression and the spatial infiltration of immune cells in PDAC patients with different survival rates. Our data demonstrate that long-term survivorship of PDAC patients is influenced by the presence of B cells in the tumor microenvironment. The role of B cells in PDAC disease is controversial. However, our findings illustrate that B cells interact with other compartments of the immune system and drive long-term survivorship in PDAC patients.

    Hosein Aziz1, Lawlaw Saida1, Jasper Dumas2,4, Andrew Stubbs2,3, Yunlei Li2,3, Casper van Eijck1,4 and Dana A. Mustafa2,4

    1 Department of Surgery, 2 Department of Pathology, 3 Division of Clinical Bioinformatics, 4 The Tumor Immuno-Pathology (TIP) Laboratory, Erasmus University Medical Center, Rotterdam, the Netherlands.


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