التفاصيل البيبلوغرافية
| العنوان: |
Investigating the immune landscape in gastric cancer |
| المؤلفون: |
Wang, Minyu |
| سنة النشر: |
2019 |
| المجموعة: |
The University of Melbourne: Digital Repository |
| مصطلحات موضوعية: |
Gastric cancer, Immune response, Tumour microenvironment, CD8+ T cells, CD4+FOXP3+ T cells, Prognosis |
| الوصف: |
© 2019 Minyu Wang ; This thesis investigates the relationship between the immunological microenvironment and clinical outcomes of patients diagnosed with gastric cancer (GC). I conducted a comprehensive study integrating immune cellular and molecular analyses of tumour tissues as well as paired peripheral bloods to investigate the role of T cells on clinical outcomes. Gene expression data from gastric tumours (n=100) and non-tumour gastric tissue (n=50) from a prospectively collected cohort (MAUGIC) was analysed using multiple bioinformatics tools to reveal that immune-related pathways and genes were enriched in gastric tumours. This enrichment emphasise T cells play a fundamental role in tumour biology and warrant detailed examination. The immune landscape of gastric cancer was based on a whole-slide multiplex immunohistochemistry (mIHC) platform which allowed both density and distance analysis of immunological components of the microenvironment. A novel algorithm measuring spatial distance relationships between cells, termed Intercellular Spatial Analysis Tool (ISAT) was developed. ISAT calculated the parameter, median intercellular nearest (MIN) distance, to reveal spatial characteristics relevant to dynamics of the tumour microenvironment. It was revealed that the EBV positive and microsatellite unstable (MSI) molecular subtypes showed a robust immune response. The difference in immune characteristics was not strong between intestinal and diffuse subtypes. The association of gastric cancer patients’ outcomes and the immune context in the tumours was further explored using mIHC in FFPE sections (n=56) and the transcriptome profiling data from paired tumours (n=40). It was discovered increased CD4+FOXP3+ T cell density in tumour correlated with prolonged survival. ISAT algorithm revealed CD4+FOXP3+ T cells clustered with CD8+ T cells rather than tumour cells. High density of CD4+FOXP3+ T cells and CD8+ T cells (High-High) predicted prolonged patient survival, and this was validated in an independent cohort ... |
| نوع الوثيقة: |
doctoral or postdoctoral thesis |
| اللغة: |
unknown |
| العلاقة: |
http://hdl.handle.net/11343/233656Test |
| الإتاحة: |
http://hdl.handle.net/11343/233656Test |
| حقوق: |
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| رقم الانضمام: |
edsbas.ABECFFB5 |
| قاعدة البيانات: |
BASE |
