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Nancy Zaarour

Title: Unleash the potential of T-cell mediated immune response within the Fallopian tube for ovarian cancer prevention.

Abstract: High-grade serous ovarian cancer (HGSC) is the most lethal histotype of ovarian cancer and most cases present with metastasis and late-stage disease. Over the last few decades, the overall survival for patients has not significantly improved, and there are limited targeted treatment options. The fallopian tube is now believed to be the origin of most high grade serous ovarian cancers. Exploring the anti-tumor potential of immune cells in the fallopian tube is essential to implement preventative strategies. In spite of documented evidence of immune cell infiltration of the connective tissue surrounding serous tubal intraepithelial carcinomas (STICs), the ovarian cancer precursor, the direct demonstration of the ability of tissue resident memory T cells (TRMs) in eliciting an anti-tumour immune response has not been previously shown. In this talk, we will discuss our recent findings showing how TRMs that reside in non-cancerous fallopian tubes recall a memory response by reacting to tumour organoids derived from omental metastases in the same patient. Moreover, these memory cells induce apoptosis in tumour-derived organoids indicating that they possess cytotoxic ability. We will also shed light on the discovery of a novel T cell subset with an immune-epithelial phenotype. Harnessing the power of TRMs could guide the design of novel vaccination strategies to prevent ovarian cancer.

 

Karl Morten

Title: Raman microspectroscopy: a new tool coming to a lab near you

Abstract: Mass spectrometry (MS) has remained the gold standard for metabolomics but requires destructive sample preparation and gives no spatial resolution within a sample. Raman spectroscopy is a label-free spectroscopy method increasingly utilised in the biological field due to overcoming the limitations of MS. Each molecule in a biological sample will have a different vibrational energy, causing differential polarisation of photons and generate a different Raman ‘fingerprint’ for each sample. For this reason, Raman has been utilised in the study of biological samples, with Raman bands able to identify important biological macromolecules, metabolites, and cell types, requiring only single cells for analysis. A clear Raman fingerprint correlating to a mitochondrial respiration (OXPHOS) or glycolysis signature could be utilised in the assessment of cell metabolism in tumours.

Through manipulation of cell culture conditions, we can generate distinct metabolic phenotypes in A549 and H460 non-small cell lung cancer lines, which are either high in OXPHOS or glycolysis. Utilising Raman spectroscopy on whole cells and isolated mitochondria from these cell lines, we show clear differences in Raman spectra, particularly in bands correlating to cytochrome c molecules and amino acids, which could be attributed to differences in metabolism This has important implications in cancer research and our understanding of tumour metabolism, with spatial assessment of metabolism within a tumour possible. Furthermore, with only single cells required rather than an invasive biopsy in patients, Raman spectroscopy could be a highly effective diagnostic tool for tumour metabolism in patients, indicating which tumours may be sensitive to metabolism targeted therapies, and allowing more individualised treatment.

Recent papers:

Developing a Blood Cell‐Based Diagnostic Test for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Using Peripheral Blood Mononuclear Cells (nih.gov)

Raman micro-spectroscopy as a tool to study immunometabolism | Biochemical Society Transactions | Portland Press