Govaerts, C. W. (2021) An in-silico-based approach to the comparative assessment of tumour-microenvironment associated immune status in brain metastases and glioblastoma. thesis, Medicine.
Full text available on request.Abstract
Widespread treatment resistance in glioblastoma and brain metastases has recently led to the investigation into the efficacy of immune-checkpoint inhibitors against these tumour types. Clinical trial data indicates that response rates differ markedly not only between glioblastoma and brain metastases as a whole, but also between brain metastases derived from different primary tumour types. This suggests tumour-type specific variation in immune status and immunogenicity. One of the most important determinants of immunogenicity is the cellular composition and functional status of the tumour microenvironment (TME). We sought to uncover the degree to which the TME was constructed differently between these tumour types and whether or not this reflected the contrast in immune status suggested by clinical trial data. We characterised the TME of RNA-microarray glioblastoma and brain metastasis samples from non-small-cell-lung-cancer (NSCLC) and breast cancer through an explorative and comparative in-silico approach. Data was downloaded from the gene-expression omnibus and was used as input into the CIBERSORT deconvolution tool, which yielded proportion values per sample for 22 haematopoietic cell types. Following this, the data was subjected to both consensus-independent component analysis and a conventional analysis of differentially expressed genes. The results indicate that substantial differences in cellular composition exist between glioblastoma and brain metastases. Our observations, such as an enhanced infiltration by M2 macrophages in glioblastoma, are largely reflective of this being an immunologically ‘colder’ tumour type. The data further suggests transcriptional differences in NSCLC and breast cancer brain metastases related to chemokine signalling and macrophage receptor co-stimulation. Our findings will form the basis for hypothesis generation and further mechanistic exploration.
| Item Type: | Thesis (UNSPECIFIED) |
|---|---|
| Supervisor name: | Kruyt, prof. dr. F. A. E. and Dijk, prof. dr. J. M. C. van |
| Faculty: | Medical Sciences |
| Date Deposited: | 24 Dec 2021 11:12 |
| Last Modified: | 24 Dec 2021 11:12 |
| URI: | https://umcg.studenttheses.ub.rug.nl/id/eprint/2916 |
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