Young Scientist Travel Award to Washington DC in 2015

ATA Scientific would like to thank all those that participated in our November 2014 Travel Award promotion. Our winner was selected by a panel from the Organising Committee of the Australasia Extracellular Vesicles conference, Cairns, 20-21 Nov 2014 where the winner was announced.

Congratulations to Dr Shu Wen Wen (QIMR Berghofer Medical Research Institute, Tumour Microenvironment Laboratory) for winning our Young Scientist Travel Award. The award includes a $2000 contribution for travel costs to attend the International Society of Extracellular Vesicles (ISEV) annual meeting, ISEV2015, 23-26 April, 2015 in Washington DC, USA

The Tumour Microenvironment Laboratory at the QIMR Berghofer Medical Research Institute focuses on how specific processes between cancer cells and surrounding non-tumour stromal cells influence carcinogenesis and its metastasis to distant organs. In particular, work aims to understand how low oxygen (hypoxic) environments and other stress conditions, changes the physiology between tumour cells and stromal cell lineages. The team aim to understand the role of hypoxia to generate receptive secondary metastatic sites. This research enables novel therapies to be generated as well as diagnostic and predictive markers to improve the outcomes of breast and lung cancer patients.

Dr Shu Wen Wen joined the Tumour Microenvironment Laboratory headed by Dr Andreas Moeller at the QIMR Berghofer Medical Research Institute, as postdoctoral researcher to continue her interest in leading metastasis research. “My research focuses on how cancer cells communicate with other parts of the body by the secretion of the small particles called exosomes. These exosomes act as messengers from the cancer to alter the behaviour and function of other cells to ultimately enhance cancer growth. Exosomes released by cancer cells represent a novel therapeutic target for cancer patients” said Dr Shu Wen Wen.

Below is a copy if the winning abstract to be presented at the ISEV 2015 conference.

“Tissue distribution of breast cancer-derived exosomes and their immune suppressive effects.

Shu Wen Wen1, Melanie Becker1, Jaclyn Sceneay1, Christina Wong1, Andreas Moller1,2 1 QIMR Berghofer Medical Research Institute 2 University of Queensland

Metastatic disease is responsible for over 90% of cancer-related deaths. Tumour progression and its systemic spread are highly dependent on the communication between cancer cells and their surrounding stroma. To date, much remains unknown about the tissue distribution of tumour-derived exosomes and their role in immunomodulation, which are important parameters defining their therapeutic potential.

To firstly understand the biodistribution of exosomes, we used optical imaging for the longitudinal tracking of exosomes derived from a highly metastatic murine breast cancer cell line (E0771) in syngeneic mice. Intravenously administered, fluorescently-labelled exosomes accumulated predominately in the lung, as well as in the spleen and bone marrow within 24 hours and up to 72 hours after injection. High specific uptake of fluorescently-labelled exosomes was particularly observed in CD11b+/Gr+ myeloid cells in the lung and lower uptake observed in CD4+ and CD8+ T-cells in the diffe rent tissues as assessed by flow cytometry. CD11b+/Gr+ cells display the characteristics of immune-suppressive Myeloid-derived Suppressor Cells (MDSCs), which we have previously shown to be modified by tumour-secreted proteins in the formation of a pre-metastatic niche. Additionally, by characterising the composition of organ-specific immune cell lineages, we identified a significant reduction in CD4+ and CD8+ T-cell populations of mice treated with breast cancer exosomes. This was accompanied by increased CD11b+/Grmed and CD11b+/Grhigh in the lung. Dose-dependent suppression of T-cell proliferation and function was further confirmed by in vitro co-culture experiments. Proteomic analysis found tumour-derived exosomes were enriched for TRAIL, B7-H4 and galectin 9, which can promote T cell apoptosis and decrease proliferation. In addition to suppressing T-cell-mediated anti-tumour functions, tumour-derived exosomes had a direct inhibitory effect on Natural Killer (NK) cell cytotoxic ity as demonstrated by chromium release assays. Taken together, our findings provide a first insight into the tissue-specific distribution of breast cancer-derived exosomes and their contribution to immune suppression by limiting T-cell and NK cell function.

This data suggests that the immune-suppressive functions of exosomes are potential targets of novel anti-cancer therapeutics in breast cancer. Additionally, it provides insights into the implications of tumour-derived exosomes for current and pre-clinical immunotherapies.”

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